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Parkinson Disease: HELP
Articles from Leuven
Based on 140 articles published since 2008

These are the 140 published articles about Parkinson Disease that originated from Leuven during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Editorial Unlocking ATP13A2/PARK9 activity. 2015

Martin, Shaun / Holemans, Tine / Vangheluwe, Peter. ·a Laboratory of Cellular Transport Systems ; Department of Cellular and Molecular Medicine; ON1 Campus Gasthuisberg ; KU Leuven ; Leuven , Belgium. ·Cell Cycle · Pubmed #26392192.

ABSTRACT: -- No abstract --

2 Editorial Can the increasing number of newly developed leucine-rich repeat kinase 2 inhibitors validate or invalidate a potential disease-modifying therapeutic approach for Parkinson's disease? 2014

Taymans, Jean-Marc. ·KU Leuven Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences , Kapucijnenvoer 33 VCTB+5 bus 7001, 3000 Leuven , Belgium +32 16 332 194 ; +32 16 336 336 ; jean-marc.taymans@med.kuleuven.be. ·Expert Opin Ther Pat · Pubmed #24875782.

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is considered an attractive therapeutic target for potential disease-modifying treatment of Parkinson's disease (PD). Both genetic and cell biological evidence have contributed to the hypothesis that LRRK2 kinase inhibition may have therapeutic potential in PD. This hypothesis was widely translated in drug discovery programs as illustrated by the growing number of patents covering newly discovered LRRK2 kinase inhibitors and emanating from at least 20 different public and private research organizations. With work still under way, this research shows the feasibility of developing potent, selective and brain permeable LRRK2 kinase inhibitors. The growing availability of these pharmacological tools should contribute to filling in the gaps in our knowledge on the safety and efficacy of LRRK2 kinase inhibition and validate/invalidate this therapeutic strategy for further development. Validation criteria should include a lack of toxic effects following long-term treatment with inhibitors as well as confirmation of target engagement in cells and animal models leading to improvement of pathological features in phenotypic assays. The state of advancement of the field of LRRK2 is such that existing biological tools and expertise can be combined with the increasing number of available LRRK2 kinase inhibitors to address these key issues.

3 Review The enteric nervous system in PD: gateway, bystander victim, or source of solutions. 2018

Shannon, Kathleen / Vanden Berghe, Pieter. ·UW School of Medicine and Public Health, Madison, WI, USA. · Lab. for Enteric NeuroScience (LENS), Translational Research of Gastrointestinal Disorder (TARGID), CHROMETA, University of Leuven, Leuven, Belgium. pieter.vandenberghe@kuleuven.be. ·Cell Tissue Res · Pubmed #29936550.

ABSTRACT: Apart from the characteristic and progressive motor- and movement-related problems, Parkinson's disease (PD) patients also suffer from several non-motor symptoms, including gastrointestinal dysfunction. The fact that the enteric nervous system (ENS) controls motility and that one of the typical PD hallmarks, α-synuclein-positive deposits, has also been found in the intestinal wall have rendered the ENS and the gut a popular subject of study in the context of PD. The possibility that these deposits could serve as an early biomarker is obviously of tremendous medical benefit but also the idea that the gut may possibly be a gateway via which the disease is initiated and progressively makes its way via the peripheral nerves to the central nervous system has increased the interest in the ENS-PD link. Furthermore, the fact that gastrointestinal symptoms are present in PD suggests that the ENS might be affected as well. However, despite a large body of literature on the topic, the actual role or the magnitude of involvement of the ENS in PD remains elusive. The multitudes of experimental approaches and animal models have complicated the interpretation of results and the outcome of different studies does not necessarily align well. In this review, we chose to highlight some elements of interest and some items of confusion, particularly those where research should be focusing. We also list a number of open questions in the field that could serve as a guideline for future, preferably concerted research.

4 Review Linking Neuroinflammation and Neurodegeneration in Parkinson's Disease. 2018

Gelders, Géraldine / Baekelandt, Veerle / Van der Perren, Anke. ·Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. ·J Immunol Res · Pubmed #29850629.

ABSTRACT: Neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a pressing burden on our developed and consequently aging society. Misfolded protein aggregates are a critical aspect of several neurodegenerative diseases. Nevertheless, several questions remain unanswered regarding the role of misfolded protein aggregates and the cause of neuronal cell death. Recently, it has been postulated that neuroinflammatory processes might play a crucial role in the pathogenesis of PD. Numerous postmortem, brain imaging, epidemiological, and animal studies have documented the involvement of the innate and adaptive immunity in neurodegeneration. Whether these inflammatory processes are directly involved in the etiology of PD or represent secondary consequences of nigrostriatal pathway injury is the subject of intensive research. Immune alterations in response to extracellular

5 Review Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. 2018

Quansah, Emmanuel / Peelaerts, Wouter / Langston, J William / Simon, David K / Colca, Jerry / Brundin, Patrik. ·Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 333 Bostwick Ave, Michigan, 49503, USA. · KU Leuven, Laboratory for Gene Therapy and Neurobiology, 3000, Leuven, Belgium. · Stanford Udall Center, Department of Pathology, Stanford University, Palo Alto, CA, USA. · Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Metabolic Solutions Development Company, Kalamazoo, MI, 49007, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 333 Bostwick Ave, Michigan, 49503, USA. patrik.brundin@vai.org. ·Mol Neurodegener · Pubmed #29793507.

ABSTRACT: Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson's disease. Failure of cellular energy metabolism has long been implicated in sporadic Parkinson's disease and recent research on rare inherited forms of Parkinson's disease have added further weight to the importance of energy metabolism in the disease pathogenesis. There exists a new class of anti-diabetic insulin sensitizers in development that inhibit the mitochondrial pyruvate carrier (MPC), a protein which mediates the import of pyruvate across the inner membrane of mitochondria. Pharmacological inhibition of the MPC was recently found to be strongly neuroprotective in multiple neurotoxin-based and genetic models of neurodegeneration which are relevant to Parkinson's disease. In this review, we summarize the neuroprotective effects of MPC inhibition and discuss the potential putative underlying mechanisms. These mechanisms involve augmentation of autophagy via attenuation of the activity of the mammalian target of rapamycin (mTOR) in neurons, as well as the inhibition of neuroinflammation, which is at least partly mediated by direct inhibition of MPC in glia cells. We conclude that MPC is a novel and potentially powerful therapeutic target that warrants further study in attempts to slow Parkinson's disease progression.

6 Review ɑ-Synuclein strains and seeding in Parkinson's disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences. 2018

Peelaerts, W / Bousset, L / Baekelandt, V / Melki, R. ·Laboratory for Neurobiology and Gene Therapy, KU Leuven, 3000, Leuven, Belgium. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, 49503, USA. · Paris-Saclay Institute of Neuroscience, CNRS, 91190, Gif-sur-Yvette, France. · Laboratory for Neurobiology and Gene Therapy, KU Leuven, 3000, Leuven, Belgium. veerle.baekelandt@kuleuven.be. ·Cell Tissue Res · Pubmed #29704213.

ABSTRACT: Several age-related neurodegenerative disorders are characterized by the deposition of aberrantly folded endogenous proteins. These proteins have prion-like propagation and amplification properties but so far appear nontransmissible between individuals. Because of the features they share with the prion protein, PrP, the characteristics of pathogenic protein aggregates in several progressive brain disorders, including different types of Lewy body diseases (LBDs), such as Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), have been actively investigated. Even though the pleomorphic nature of these syndromes might suggest different underlying causes, ɑ-synuclein (ɑSyn) appears to play an important role in this heterogeneous group of diseases (the synucleinopathies). An attractive hypothesis is that different types of ɑSyn protein assemblies have a unique and causative role in distinct synucleinopathies. We will discuss the recent research progress on ɑSyn assemblies involved in PD, MSA and DLB; their behavior as strains; current spreading hypotheses; their ability to seed centrally and peripherally; and their implication for disease pathogenesis.

7 Review LRRK2 Phosphorylation: Behind the Scenes. 2018

De Wit, Tina / Baekelandt, Veerle / Lobbestael, Evy. ·1 Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. ·Neuroscientist · Pubmed #29385885.

ABSTRACT: Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are known today as the most common genetic cause of Parkinson's disease (PD). LRRK2 is a large protein that is hypothesized to regulate other proteins as a scaffold in downstream signaling pathways. This is supported by the multiple domain composition of LRRK2 with several protein-protein interaction domains combined with kinase and GTPase activity. LRRK2 is highly phosphorylated at sites that are strictly controlled by upstream regulators, including its own kinase domain. In cultured cells, most pathogenic mutants display increased autophosphorylation at S1292, but decreased phosphorylation at sites controlled by other kinases. We only begin to understand how LRRK2 phosphorylation is regulated and how this impacts its physiological and pathological function. Intriguingly, LRRK2 kinase inhibition, currently one of the most prevailing disease-modifying therapeutic strategies for PD, induces LRRK2 dephosphorylation at sites that are also dephosphorylated in pathogenic variants. In addition, LRRK2 kinase inhibition can induce LRRK2 protein degradation, which might be related to the observed inhibitor-induced adverse effects on the lung in rodents and non-human primates, as it resembles the lung pathology in LRRK2 knock-out animals. In this review, we will provide an overview of how LRRK2 phosphorylation is regulated and how this complex regulation relates to several molecular and cellular features of LRRK2.

8 Review Cueing for people with Parkinson's disease with freezing of gait: A narrative review of the state-of-the-art and novel perspectives. 2018

Ginis, Pieter / Nackaerts, Evelien / Nieuwboer, Alice / Heremans, Elke. ·KU Leuven, Department of Rehabilitation Sciences, Neuromotor Rehabilitation Research Group, Tervuursevest 101 box 1501, 3000 Leuven, Belgium. Electronic address: pieter.ginis@kuleuven.be. · KU Leuven, Department of Rehabilitation Sciences, Neuromotor Rehabilitation Research Group, Tervuursevest 101 box 1501, 3000 Leuven, Belgium. ·Ann Phys Rehabil Med · Pubmed #28890341.

ABSTRACT: Freezing, which manifests during gait and other movements, is an incapacitating motor symptom experienced by many patients with Parkinson's disease (PD). In rehabilitation, auditory and visual cueing methods are commonly applied to evoke a more goal-directed type of motor control and, as such, reduce freezing severity in patients with PD. In this narrative review, we summarize the current evidence regarding the effects of external cueing in patients with PD with freezing of gait (FOG) and provide suggestions on how to further improve cueing effectiveness with emerging technological developments. For this paper, we reviewed 24 articles describing the assessment of the effects of cues in patients with FOG (n=354). Because these studies mostly involved quasi-experimental designs, no methodological analysis was undertaken. In general, the evidence suggests that cue-augmented training can reduce FOG severity, improve gait parameters and improve upper-limb movements immediately after training. However, findings were not univocal, and long-term consolidation and transfer of the effects appear to be hampered specifically in this subgroup. With the increasing use of wearable technology, new possibilities are allowing for adapting the cue type, cue content and dose of cues to the needs of individual patients, which may boost the clinical use and efficiency of cued training in PD patients with FOG.

9 Review Clinical balance scales indicate worse postural control in people with Parkinson's disease who exhibit freezing of gait compared to those who do not: A meta-analysis. 2017

Bekkers, Esther M J / Dijkstra, Bauke W / Dockx, Kim / Heremans, Elke / Verschueren, Sabine M P / Nieuwboer, Alice. ·Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Belgium. Electronic address: esther.bekkers@kuleuven.be. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Belgium. · Research Group for Musculoskeletal Research, Department of Rehabilitation Sciences, KU Leuven, Belgium. ·Gait Posture · Pubmed #28544951.

ABSTRACT: Postural instability and freezing of gait (FOG) are key features of Parkinson's disease (PD) that are closely related to falls. Uncovering the postural control differences between individuals with and without FOG contributes to our understanding of the relationship between these phenomena. The objective of this meta-analysis was to investigate whether postural control deficits, as detected by clinical balance scales, were more apparent in FOG+ compared to FOG-. Furthermore, we aimed to identify whether different scales were equally sensitive to detect postural control deficits and whether medication affected postural control differentially in each subgroup. Relevant articles were identified via five electronic databases. We performed a meta-analysis on nine studies which reported clinical balance scale scores in 249 freezers and 321 non-freezers. Methodological analysis showed that in 5/9 studies disease duration differed between subgroups. Despite this drawback, postural control was found to be significantly worse in FOG+ compared to FOG-. All included clinical balance scales were found to be sufficiently sensitive to detect the postural control differences. Levodopa did not differentially affect postural control (p=0.21), as in both medication states FOG+ had worse postural stability than FOG-. However, this finding warrants a cautious interpretation given the limitations of the studies included. From subscore analysis, we found that reactive and dynamic postural control were the most affected postural control systems in FOG+. We conclude that our findings provide important evidence for pronounced postural instability in individuals with FOG, which can be easily picked up with clinical evaluation tools. Posturographic measures in well-matched subgroups are needed to highlight the exact nature of these deficits.

10 Review Yeast models of Parkinson's disease-associated molecular pathologies. 2017

Tenreiro, Sandra / Franssens, Vanessa / Winderickx, Joris / Outeiro, Tiago Fleming. ·CEDOC-Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal. · Department of Biology, Functional Biology, KU Leuven, 3001 Heverlee, Belgium. · CEDOC-Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Department of Neurodegeneration and Restorative Research, University Medical Center Goettingen, Goettingen, Germany. Electronic address: touteir@gwdg.de. ·Curr Opin Genet Dev · Pubmed #28232272.

ABSTRACT: The aging of the human population is resulting in an increase in the number of people afflicted by neurodegenerative disorders such as Parkinson's disease (PD), creating tremendous socio-economic challenges. This requires the urgent for the development of effective therapies, and of tools for early diagnosis of the disease. However, our understanding of the molecular mechanisms underlying PD pathogenesis is still incomplete, hampering progress in those areas. In recent years, the progression made in genetics has considerably contributed to our knowledge, by identifying several novel PD genes. Furthermore, many cellular and animal models have proven their value to decipher pathways involved in PD development. In this review we highlight the value of the yeast Saccharomyces cerevisiae as a model for PD. This unicellular eukaryote has contributed to our understanding of the cellular mechanisms targeted by most important PD genes and offers an excellent tool for discovering novel players via powerful and informative high throughput screens that accelerate further validation in more complex models.

11 Review Virtual reality for rehabilitation in Parkinson's disease. 2016

Dockx, Kim / Bekkers, Esther Mj / Van den Bergh, Veerle / Ginis, Pieter / Rochester, Lynn / Hausdorff, Jeffrey M / Mirelman, Anat / Nieuwboer, Alice. ·Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, Postbus 1501, Leuven, Belgium, 3001. · Institute for Ageing and Health, Newcastle University, Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle upon Tyne, UK, NE4 5PL. · Center for the Study of Movement, Cognition and Morbility, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel, 64239. · Department of Neurology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, Israel, 64239. ·Cochrane Database Syst Rev · Pubmed #28000926.

ABSTRACT: BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that is best managed by a combination of medication and regular physiotherapy. In this context, virtual reality (VR) technology is proposed as a new rehabilitation tool with a possible added value over traditional physiotherapy approaches. It potentially optimises motor learning in a safe environment, and by replicating real-life scenarios could help improve functional activities of daily living. OBJECTIVES: The objective of this review was to summarise the current best evidence for the effectiveness of VR interventions for the rehabilitation of people with PD in comparison with 1) active interventions, and 2) passive interventions. Our primary goal was to determine the effect of VR training on gait and balance. Secondary goals included examining the effects of VR on global motor function, activities of daily living, quality of life, cognitive function, exercise adherence, and the occurrence of adverse events. SEARCH METHODS: We identified relevant articles through electronic searches of the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, Embase, CINAHL, the Physiotherapy Evidence Database (PEDro), online trials registers, and by handsearching reference lists. We carried out all searches up until 26 November 2016. SELECTION CRITERIA: We searched for randomised and quasi-randomised controlled trials of VR exercise interventions in people with PD. We included only trials where motor rehabilitation was the primary goal. DATA COLLECTION AND ANALYSIS: Two review authors independently searched for trials that corresponded to the predefined inclusion criteria. We independently extracted and assessed all data for methodological quality. A third review author was responsible for conflict resolution when required. MAIN RESULTS: We included 8 trials involving 263 people with PD in the review. Risk of bias was unclear or high for all but one of the included studies. Study sample sizes were small, and there was a large amount of heterogeneity between trials with regard to study design and the outcome measures used. As a result, we graded the quality of the evidence as low or very low. Most of the studies intended to improve motor function using commercially available devices, which were compared with physiotherapy. The interventions lasted for between 4 and 12 weeks.In comparison to physiotherapy, VR may lead to a moderate improvement in step and stride length (standardised mean difference (SMD) 0.69, 95% confidence interval (CI) 0.30 to 1.08; 3 studies; 106 participants; low-quality evidence). VR and physiotherapy interventions may have similar effects on gait (SMD 0.20, 95% CI -0.14 to 0.55; 4 studies; 129 participants; low-quality evidence), balance (SMD 0.34, 95% CI -0.04 to 0.71; 5 studies; 155 participants; low-quality evidence), and quality of life (mean difference 3.73 units, 95% CI -2.16 to 9.61; 4 studies; 106 participants). VR interventions did not lead to any reported adverse events, and exercise adherence did not differ between VR and other intervention arms.The evidence available comparing VR exercise with a passive control was more limited. The evidence for the main outcomes of interest was of very low quality due to the very small sample sizes of the two studies available for this comparison. AUTHORS' CONCLUSIONS: We found low-quality evidence of a positive effect of short-term VR exercise on step and stride length. VR and physiotherapy may have similar effects on gait, balance, and quality of life. The evidence available comparing VR with passive control interventions was more limited. Additional high-quality, large-scale studies are needed to confirm these findings.

12 Review PARL: The mitochondrial rhomboid protease. 2016

Spinazzi, Marco / De Strooper, Bart. ·VIB Center for the Biology of Disease, O&N4 Herestraat 49 box 602, 3000, Leuven, Belgium; KU Leuven Center for Human Genetics, O&N4 Herestraat 49 box 602, 3000, Leuven, Belgium. · VIB Center for the Biology of Disease, O&N4 Herestraat 49 box 602, 3000, Leuven, Belgium; KU Leuven Center for Human Genetics, O&N4 Herestraat 49 box 602, 3000, Leuven, Belgium; UCL Institute of Neurology, University College London, WC1N 3BG, UK. Electronic address: bart.destrooper@cme.vib-kuleuven.be. ·Semin Cell Dev Biol · Pubmed #27502471.

ABSTRACT: The rhomboid family comprises evolutionary conserved intramembrane proteases involved in a wide spectrum of biologically relevant activities. A mitochondrion-localized rhomboid, called PARL in mammals, and conserved in yeast and Drosophila as RBD1/PCP1 and rho-7, respectively, plays an indispensable role in cell homeostasis as illustrated by the severe phenotypes caused by its genetic ablation in the various investigated species. Although several substrates of PARL have been proposed to explain these phenotypes, there remains a lot of controversy in this important area of research. We review here the putative functions and substrates of PARL and its orthologues in different species, highlighting areas of uncertainty, and discuss its potential involvement in some prevalent diseases such as type II diabetes and Parkinson's disease.

13 Review Disability Rating Scales in Parkinson's Disease: Critique and Recommendations. 2016

Shulman, Lisa M / Armstrong, Melissa / Ellis, Terry / Gruber-Baldini, Ann / Horak, Fay / Nieuwboer, Alice / Parashos, Sotirios / Post, Bart / Rogers, Mark / Siderowf, Andrew / Goetz, Christopher G / Schrag, Anette / Stebbins, Glenn T / Martinez-Martin, Pablo. ·Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA. lshulman@som.umaryland.edu. · Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Department of Physical Therapy & Athletic Training, Boston University, Boston, Massachusetts, USA. · Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Department of Neurology, Oregon Health and Science University and Portland VA Medical System, Portland, Oregon, USA. · Department of Rehabilitation Science, KU Leuven-University of Leuven, Heverlee, Belgium. · Struthers Parkinson's Center, Golden Valley, Minnesota, USA. · Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Physical Therapy & Rehabilitation, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Avid Radiopharmaceuticals, Philadelphia, PA, USA. · Department of Neurology, Rush University Medical Center, Chicago, USA. · UCL Institute of Neurology, University College London, UK. · National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Mov Disord · Pubmed #27193358.

ABSTRACT: INTRODUCTION: PD is associated with impairments that progress over time to disability. A large number of disability scales exist with little information on the best choice in PD. METHODS: Following methodology adopted by the International Parkinson and Movement Disorder Society Task Force, a review of disability scales used in PD was completed. Based on prespecified criteria, the review categorized scales into: "Recommended"; "Recommended with Further Validation in PD Required" when well-validated scales have not been specifically tested for clinimetric properties in PD; "Suggested"; and "Listed." RESULTS: Twenty-nine disability instruments were identified with nine scales fulfilling criteria for "Recommended" and 7 "Recommended with Further Validation in PD Required." Eight scales are "Suggested" and five scales are "Listed" for use in PD. The nine Recommended scales (Functional Status Questionnaire, Lawton-Brody Activities of Daily Living, Nottingham Activities of Daily Living, Schwab and England Activities of Daily Living, Self-Assessment PD Disability, Short Parkinson's Evaluation Scale/Scales for Outcomes in PD, Unified PD Rating Scale-II: Activities of Daily Living, Movement Disorders Society UPDRS Motor Experiences of Daily Living, PROMIS CONCLUSION: Many disability measures are available and recommended for application in PD. The Task Force does not recommend the development of a new scale. Selection of the most appropriate instrument for a particular objective requires consideration of the characteristics of each scale and the goals of the assessment. © 2016 International Parkinson and Movement Disorder Society.

14 Review Risk Factors for Malnutrition in Older Adults: A Systematic Review of the Literature Based on Longitudinal Data. 2016

Fávaro-Moreira, Nádia Cristina / Krausch-Hofmann, Stefanie / Matthys, Christophe / Vereecken, Carine / Vanhauwaert, Erika / Declercq, Anja / Bekkering, Geertruida Elsiena / Duyck, Joke. ·Population Studies in Oral Health, Department of Oral Health Sciences. · Department of Clinical and Experimental Medicine, Clinical Nutrition Unit, Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium; · University College Leuven-Limburg, Knowledge and Information Center FOOD, Leuven, Belgium; and. · Department of Clinical and Experimental Medicine, University College Leuven-Limburg, Knowledge and Information Center FOOD, Leuven, Belgium; and. · LUCAS, Centre for Care Research and Consultancy. · Belgian Center for Evidence Based Medicine, Leuven, Belgium. · Population Studies in Oral Health, Department of Oral Health Sciences, BIOMAT Research Cluster, Department of Oral Health Sciences, Katholieke Universiteit Leuven, Leuven, Belgium; joke.duyck@med.kuleuven.be. ·Adv Nutr · Pubmed #27184278.

ABSTRACT: The present systematic review critically examines the available scientific literature on risk factors for malnutrition in the older population (aged ≥65 y). A systematic search was conducted in MEDLINE, reviewing reference lists from 2000 until March 2015. The 2499 papers identified were subjected to inclusion criteria that evaluated the study quality according to items from validated guidelines. Only papers that provided information on a variable's effect on the development of malnutrition, which requires longitudinal data, were included. A total of 6 longitudinal studies met the inclusion criteria and were included in the systematic review. These studies reported the following significant risk factors for malnutrition: age (OR: 1.038; P = 0.045), frailty in institutionalized persons (β: 0.22; P = 0.036), excessive polypharmacy (β: -0.62; P = 0.001), general health decline including physical function (OR: 1.793; P = 0.008), Parkinson disease (OR: 2.450; P = 0.047), constipation (OR: 2.490; P = 0.015), poor (OR: 3.30; P value not given) or moderate (β: -0.27; P = 0.016) self-reported health status, cognitive decline (OR: 1.844; P = 0.001), dementia (OR: 2.139; P = 0.001), eating dependencies (OR: 2.257; P = 0.001), loss of interest in life (β: -0.58; P = 0.017), poor appetite (β: -1.52; P = 0.000), basal oral dysphagia (OR: 2.72; P = 0.010), signs of impaired efficacy of swallowing (OR: 2.73; P = 0.015), and institutionalization (β: -1.89; P < 0.001). These risk factors for malnutrition in older adults may be considered by health care professionals when developing new integrated assessment instruments to identify older adults' risk of malnutrition and to support the development of preventive and treatment strategies.

15 Review Technology in Parkinson's disease: Challenges and opportunities. 2016

Espay, Alberto J / Bonato, Paolo / Nahab, Fatta B / Maetzler, Walter / Dean, John M / Klucken, Jochen / Eskofier, Bjoern M / Merola, Aristide / Horak, Fay / Lang, Anthony E / Reilmann, Ralf / Giuffrida, Joe / Nieuwboer, Alice / Horne, Malcolm / Little, Max A / Litvan, Irene / Simuni, Tanya / Dorsey, E Ray / Burack, Michelle A / Kubota, Ken / Kamondi, Anita / Godinho, Catarina / Daneault, Jean-Francois / Mitsi, Georgia / Krinke, Lothar / Hausdorff, Jeffery M / Bloem, Bastiaan R / Papapetropoulos, Spyros / Anonymous1111027. ·James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA. alberto.espay@uc.edu. · Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA. · Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tübingen, Germany. · DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. · Davis Phinney Foundation for Parkinson's, Boulder, Colorado, USA. · Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. · Digital Sports Group, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. · Department of Neuroscience "Rita Levi Montalcini", Città della salute e della scienza di Torino, Torino, Italy. · Department of Neurology, Oregon Health & Science University, Portland VA Medical System, Portland, Oregon. · APDM, Inc., Portland, Oregon, USA. · Morton and Gloria Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · George-Huntington-Institute, Muenster, Germany. · Department of Radiology, University of Muenster, Muenster, Germany. · Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. · Great Lakes NeuroTechnologies, Cleveland, Ohio, USA. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium. · Global Kinetics Corporation & Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. · Department of Mathematics, Aston University, Birmingham, UK. · Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. · Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. · Michael J Fox Foundation for Parkinson's Research, New York City, New York, USA. · Department of Neurology, National Institute of Clinical Neurosciences, Budapest, Hungary. · Center of Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal. · Apptomics LLC, Wellesley, Massachusetts, USA. · Medtronic Neuromodulation, Minneapolis, Minnesota, USA. · Sackler School of Medicine, Tel Aviv University and Center for the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, the Netherlands. · Massachusetts General Hospital, Boston, Massachusetts, USA. ·Mov Disord · Pubmed #27125836.

ABSTRACT: The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

16 Review Membrane Lipids in Presynaptic Function and Disease. 2016

Lauwers, Elsa / Goodchild, Rose / Verstreken, Patrik. ·Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium; VIB Center for the Biology of Disease, Leuven Institute for Neurodegenerative Disease, Herestraat 49, Bus 602, 3000 Leuven, Belgium. Electronic address: elsa.lauwers@cme.vib-kuleuven.be. · Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium; VIB Center for the Biology of Disease, Leuven Institute for Neurodegenerative Disease, Herestraat 49, Bus 602, 3000 Leuven, Belgium. Electronic address: rose.goodchild@cme.vib-kuleuven.be. · Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium; VIB Center for the Biology of Disease, Leuven Institute for Neurodegenerative Disease, Herestraat 49, Bus 602, 3000 Leuven, Belgium. Electronic address: patrik.verstreken@cme.vib-kuleuven.be. ·Neuron · Pubmed #27054615.

ABSTRACT: Lipids are the most abundant organic compounds in the brain. The brain has a unique lipidome, and changes in lipid concentration, organization, and metabolism are associated with many neuronal diseases. Here, we discuss recent advances in understanding presynaptic membrane lipid organization, centered on illustrative examples of how the lipids themselves regulate membrane trafficking and control protein activity. This insight highlights that presynaptic terminals are membrane-remodeling machines and that cooperation between lipid and protein molecules underlies presynaptic activity.

17 Review Measurement instruments to assess posture, gait, and balance in Parkinson's disease: Critique and recommendations. 2016

Bloem, Bastiaan R / Marinus, Johan / Almeida, Quincy / Dibble, Lee / Nieuwboer, Alice / Post, Bart / Ruzicka, Evzen / Goetz, Christopher / Stebbins, Glenn / Martinez-Martin, Pablo / Schrag, Anette / Anonymous5310860. ·Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Dept. of Neurology, Nijmegen, The Netherlands. bas.bloem@radboudumc.nl. · Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands. · Sun Life Financial Movement Disorders Research & Rehabilitation Centre; Department of Kinesiology & Physical Education, Wilfrid Laurier University, Waterloo, Ontario, Canada. · University of Utah, Department of Physical Therapy, Salt Lake City, Utah, USA. · KU Leuven, University of Leuven, Department of Rehabilitation Sciences, Leuven, Belgium. · Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Dept. of Neurology, Nijmegen, The Netherlands. · 1st Faculty of Medicine and General University Hospital, Dept. of Neurology and Centre of Clinical Neuroscience, Charles University, Prague, Czech Republic. · Department of Neurological Services, Rush University School of Medicine, Chicago, Illinois, USA. · Alzheimer Center Reina Sofia Foundation and CIBERNED, Carlos III Institute of Health, Madrid, Spain. · UCL Institute of Neurology, University College, London, UK. ·Mov Disord · Pubmed #26945525.

ABSTRACT: BACKGROUND: Disorders of posture, gait, and balance in Parkinson's disease (PD) are common and debilitating. This MDS-commissioned task force assessed clinimetric properties of existing rating scales, questionnaires, and timed tests that assess these features in PD. METHODS: A literature review was conducted. Identified instruments were evaluated systematically and classified as "recommended," "suggested," or "listed." Inclusion of rating scales was restricted to those that could be used readily in clinical research and practice. RESULTS: One rating scale was classified as "recommended" (UPDRS-derived Postural Instability and Gait Difficulty score) and 2 as "suggested" (Tinetti Balance Scale, Rating Scale for Gait Evaluation). Three scales requiring equipment (Berg Balance Scale, Mini-BESTest, Dynamic Gait Index) also fulfilled criteria for "recommended" and 2 for "suggested" (FOG score, Gait and Balance Scale). Four questionnaires were "recommended" (Freezing of Gait Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, Survey of Activities, and Fear of Falling in the Elderly-Modified). Four tests were classified as "recommended" (6-minute and 10-m walk tests, Timed Up-and-Go, Functional Reach). CONCLUSION: We identified several questionnaires that adequately assess freezing of gait and balance confidence in PD and a number of useful clinical tests. However, most clinical rating scales for gait, balance, and posture perform suboptimally or have been evaluated insufficiently. No instrument comprehensively and separately evaluates all relevant PD-specific gait characteristics with good clinimetric properties, and none provides separate balance and gait scores with adequate content validity for PD. We therefore recommend the development of such a PD-specific, easily administered, comprehensive gait and balance scale that separately assesses all relevant constructs. © 2016 International Parkinson and Movement Disorder Society.

18 Review ɑ-Synuclein strains and the variable pathologies of synucleinopathies. 2016

Peelaerts, Wouter / Baekelandt, Veerle. ·Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. · Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. Veerle.Baekelandt@med.kuleuven.be. ·J Neurochem · Pubmed #26924014.

ABSTRACT: Several decades ago, a mysterious transmissible agent was found responsible for a group of progressive and lethal encephalopathies affecting the nervous system of both animals and humans. This infectious agent showed a strain-encoded manner of inheritance even though it lacked nucleic acids. The identification of infectious proteins resolved this apparent conundrum. Misfolded infectious protein particles, or prions, were found to exist as conformational isomers with a unique fingerprint that can be faithfully passaged to next generations. Protein-based strain-encoded inheritance is characterized by strain-specific infectivity and symptomatology. It is found in diverse organisms, such as yeast, fungi, and mammals. Now, this concept is revisited to examine the pathological role of amyloid proteins involved in neurodegenerative diseases where it might underlie certain types of dementia and motor-related neurodegenerative disorders. Given the discovery of the SNCA gene and the identification of its gene product, ɑ-synuclein (ɑ-SYN), as the main histopathological component of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, the scientific community was left puzzled by the fact that a single protein appeared to be involved in different diseases with diverging clinical phenotypes. Recent studies are now indicating that ɑ-SYN may act in a way similar to prions and that ɑ-SYN misfolded structural variants may behave as strains with distinct biochemical and functional properties inducing specific phenotypic traits, which might finally provide an explanation for the clinical heterogeneity observed between Parkinson's disease, MSA, and dementia with Lewy bodies patients. These crucial new findings may pave the way for unexplored therapeutic avenues and identification of new potential biomarkers. Parkinson's disease and other synucleinopathies share ɑ-synuclein deposits as a common histopathological hallmark. New and ongoing developments are now showing that variations in the aggregation process and the formation of ɑ-synuclein strains may be paralleled by the development of distinct synucleinopathies. Here, we review the recent developments and the role of strains in synucleinopathies. This article is part of a special issue on Parkinson disease.

19 Review Transcranial direct current stimulation in Parkinson's disease: Neurophysiological mechanisms and behavioral effects. 2015

Broeder, Sanne / Nackaerts, Evelien / Heremans, Elke / Vervoort, Griet / Meesen, Raf / Verheyden, Geert / Nieuwboer, Alice. ·Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. Electronic address: sanne.broeder@faber.kuleuven.be. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. Electronic address: evelien.nackaerts@faber.kuleuven.be. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. Electronic address: elke.heremans@faber.kuleuven.be. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. Electronic address: griet.vervoort@faber.kuleuven.be. · Movement Control and Neuroplasticity Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium; REVAL Rehabilitation Research Centre, Biomedical Research Institute, Hasselt University, Agoralaan Building A, B-3590 Hasselt, Belgium. Electronic address: raf.meesen@uhasselt.be. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. Electronic address: geert.verheyden@faber.kuleuven.be. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. Electronic address: alice.nieuwboer@faber.kuleuven.be. ·Neurosci Biobehav Rev · Pubmed #26297812.

ABSTRACT: Recent research has highlighted the potential of transcranial direct current stimulation (tDCS) to complement rehabilitation effects in the elderly and in patients with neurological diseases, including Parkinson's disease (PD). TDCS can modulate cortical excitability and enhance neurophysiological mechanisms that compensate for impaired learning in PD. The objective of this systematic review is to provide an overview of the effects of tDCS on neurophysiological and behavioral outcome measures in PD patients, both as a stand-alone and as an adjunctive therapy. We systematically reviewed the literature published throughout the last 10 years. Ten studies were included, most of which were sham controlled. Results confirmed that tDCS applied to the motor cortex had significant results on motor function and to a lesser extent on cognitive tests. However, the physiological mechanism underlying the long-term effects of tDCS on cortical excitability in the PD brain are still unclear and need to be clarified in order to apply this technique optimally to a wider population in the different disease stages and with different medication profiles.

20 Review Dual tasking in Parkinson's disease: should we train hazardous behavior? 2015

Strouwen, Carolien / Molenaar, Esther A L M / Münks, Liesbeth / Keus, Samyra H J / Bloem, Bastiaan R / Rochester, Lynn / Nieuwboer, Alice. ·a 1 KU Leuven - University of Leuven, Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation, Tervuursevest 101 bus 1501, 3001 Leuven, Belgium. ·Expert Rev Neurother · Pubmed #26289490.

ABSTRACT: Dual-task (DT) circumstances aggravate gait disorders in Parkinson's disease (PD) and are associated with an increased risk of falling and reduced functional mobility. Clinical rehabilitation guidelines for PD consider DT interventions as potentially hazardous and recommend avoiding them in daily life. The current article challenges this notion and addresses the necessity of implementing DT training in PD. First, underlying reasons for DT interference in PD and current theoretical models are discussed. Subsequently, different training approaches to tackle DT difficulties are put forward. Finally, the effectiveness and limitations of DT training in PD are reviewed. We conclude that there is a need for DT interventions in PD and recommend randomized, power-based studies to further test their efficacy.

21 Review PINK1 activation-turning on a promiscuous kinase. 2015

Aerts, Liesbeth / De Strooper, Bart / Morais, Vanessa A. ·*Center for Human Genetics, LIND and KU Leuven, O&N1 Herestraat 49 box 602, 3000 Leuven, Belgium. ·Biochem Soc Trans · Pubmed #25849930.

ABSTRACT: PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] is a serine/threonine kinase targeted to mitochondria and implicated in early-onset recessive Parkinson's disease (PD). Through the phosphorylation of its downstream targets, PINK1 regulates multiple mitochondrial processes, including ATP production, stress-response and mitochondrial dynamics and quality control. The orchestration of such a wide array of functions by an individual kinase requires a fine-tuned and versatile regulation of its activity. PINK1 proteolytic processing, trafficking and localization, as well as different post-translational modifications, affect its activity and function. Unravelling the regulatory mechanisms of PINK1 is essential for a full comprehension of its kinase function in health and disease.

22 Review Stimulation of electron transport as potential novel therapy in Parkinson's disease with mitochondrial dysfunction. 2015

Vos, Melissa / Verstreken, Patrik / Klein, Christine. ·*Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. · †VIB Center for the Biology of Disease, Leuven, Belgium. ·Biochem Soc Trans · Pubmed #25849929.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by the loss of dopaminergic neurons. This loss of dopaminergic neurons is the pathological hallmark of the disease that results in the characteristic motor syndrome. Restoration of dopamine levels is the basis of current therapy; however, this does not tackle the cause of the disease. While the aetiology of PD remains mostly elusive, mitochondrial dysfunction has been linked to (at least) part of the PD cases. In this review we discuss recent findings in Drosophila melanogaster showing that stimulation of the electron transport chain is beneficial for PD fly models showing Complex I defects and discuss the possible clinical applications of these findings.

23 Review Flies with Parkinson's disease. 2015

Vanhauwaert, Roeland / Verstreken, Patrik. ·VIB Center for the Biology of Disease, KU Leuven, Herestraat 49,3000 Leuven, Belgium; Laboratory of Neuronal Communication, Leuven Institute for Neurodegenerative Disease (LIND), Center for Human Genetics, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. ·Exp Neurol · Pubmed #25708988.

ABSTRACT: Parkinson's disease is an incurable neurodegenerative disease. Most cases of the disease are of sporadic origin, but about 10% of the cases are familial. The genes thus far identified in Parkinson's disease are well conserved. Drosophila is ideally suited to study the molecular neuronal cell biology of these genes and the pathogenic mutations in Parkinson's disease. Flies reproduce quickly, and their elaborate genetic tools in combination with their small size allow researchers to analyze identified cells and neurons in large numbers of animals. Furthermore, fruit flies recapitulate many of the cellular and molecular defects also seen in patients, and these defects often result in clear locomotor and behavioral phenotypes, facilitating genetic modifier screens. Hence, Drosophila has played a prominent role in Parkinson's disease research and has provided invaluable insight into the molecular mechanisms of this disease.

24 Review Therapeutic strategies in Parkinson's disease: what we have learned from animal models. 2015

Valadas, Jorge S / Vos, Melissa / Verstreken, Patrik. ·VIB Center for the Biology of Disease; Department of Human Genetics, Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven, Leuven, Belgium. ·Ann N Y Acad Sci · Pubmed #25515068.

ABSTRACT: Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra, as well as in other brain areas. The currently available dopamine replacement therapy provides merely symptomatic benefit and is ineffective because habituation and side effects arise relatively quickly. Studying the genetic forms of PD in animal models provides novel insight that allows targeting of specific aspects of this heterogenic disease more specifically. Among others, two important cellular deficits are associated with PD; these deficits relate to (1) synaptic transmission and vesicle trafficking, and (2) mitochondrial function, relating respectively to the dominant and recessive mutations in PD-causing genes. With increased knowledge of PD, the possibility of identifying an efficient, long-lasting treatment is becoming more conceivable, but this can only be done with an increased knowledge of the specific affected cellular mechanisms. This review discusses how discoveries in animal models of PD have clarified the therapeutic potential of pathways disrupted in PD, with a specific focus on synaptic transmission, vesicle trafficking, and mitochondrial function.

25 Review Viral vector-based models of Parkinson's disease. 2015

Van der Perren, Anke / Van den Haute, Chris / Baekelandt, Veerle. ·Katholieke Universiteit Leuven, Leuven, Belgium, Anke.VanderPerren@med.kuleuven.be. ·Curr Top Behav Neurosci · Pubmed #24839101.

ABSTRACT: In order to study the molecular pathways of Parkinson's disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models as an alternative to toxin-based models. Viral vector-mediated loco-regional gene delivery provides an attractive way to express transgenes in the central nervous system. Several vector systems based on various viruses have been developed. In this chapter, we give an overview of the different viral vector systems used for targeting the CNS. Further, we describe the different viral vector-based PD models currently available based on overexpression strategies for autosomal dominant genes such as α-synuclein and LRRK2, and knockout or knockdown strategies for autosomal recessive genes, such as parkin, DJ-1, and PINK1. Models based on overexpression of α-synuclein are the most prevalent and extensively studied, and therefore the main focus of this chapter. Many efforts have been made to increase the expression levels of α-synuclein in the dopaminergic neurons. The best α-synuclein models currently available have been developed from a combined approach using newer AAV serotypes and optimized vector constructs, production, and purification methods. These third-generation α-synuclein models show improved face and predictive validity, and therefore offer the possibility to reliably test novel therapeutics.