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Parkinson Disease: HELP
Articles from Alabama
Based on 178 articles published since 2008
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These are the 178 published articles about Parkinson Disease that originated from Alabama during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Editorial What would Dr. James parkinson think today? Mutations in beta-glucocerebrosidase and risk of Parkinson's disease. 2017

Standaert, David G. ·Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Mov Disord · Pubmed #29068500.

ABSTRACT: -- No abstract --

2 Editorial Biomarkers in Parkinson's disease: From pathophysiology to early diagnosis. 2016

Calabresi, Paolo / Standaert, David G / Chiasserini, Davide / Parnetti, Lucilla. ·Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy. · IRCCS Fondazione Santa Lucia, Rome, Italy. · Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Mov Disord · Pubmed #27245116.

ABSTRACT: -- No abstract --

3 Editorial Identification of bona-fide LRRK2 kinase substrates. 2016

West, Andrew B / Cookson, Mark R. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA. · Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. ·Mov Disord · Pubmed #27126091.

ABSTRACT: -- No abstract --

4 Editorial Reaping what you sow: Cross-seeding between aggregation-prone proteins in neurodegeneration. 2014

Yacoubian, Talene A / Standaert, David G. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Mov Disord · Pubmed #24395732.

ABSTRACT: -- No abstract --

5 Editorial Metabolomics and the search for biomarkers in Parkinson's disease. 2013

Amara, Amy W / Standaert, David G. ·Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Mov Disord · Pubmed #24105981.

ABSTRACT: -- No abstract --

6 Review Prion-like propagation of pathology in Parkinson disease. 2018

Volpicelli-Daley, Laura / Brundin, Patrik. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States. · Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, MI, United States. Electronic address: Patrik.Brundin@vai.org. ·Handb Clin Neurol · Pubmed #29887143.

ABSTRACT: Over 100 years ago, Lewy bodies and Lewy neurites were defined as a pathologic hallmark of Parkinson disease. Eighty years later, α-synuclein was found to be the primary component of these inclusions. Emerging evidence suggests that α-synuclein pathology propagates across interconnected networks throughout the nervous system in a prion-like manner. Pathologic α-synuclein seeds aggregation of native α-synuclein, resulting in the formation of insoluble inclusions. These seeds can propagate within the neuron and to interconnected neurons, resulting in the spread of pathology throughout the brain. Here, we discuss how the findings that α-synuclein pathology spreads throughout the nervous system has revolutionized our understanding about Parkinson disease pathogenesis and resulted in the development of novel therapeutic strategies to halt disease progression.

7 Review Mitochondrial function and autophagy: integrating proteotoxic, redox, and metabolic stress in Parkinson's disease. 2018

Zhang, Jianhua / Culp, Matilda Lillian / Craver, Jason G / Darley-Usmar, Victor. ·Center for Free Radical Biology, Birmingham, Alabama, USA. · Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Veterans Affairs, Birmingham VA Medical Center, Birmingham, Alabama, USA. ·J Neurochem · Pubmed #29341130.

ABSTRACT: Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis. Indeed, data obtained from genetic and genome association studies have implicated interactive contributions of genes controlling protein quality control and metabolism. For example, loss of key proteins that are responsible for clearance of dysfunctional mitochondria through a process called mitophagy has been found to cause PD, and a significant proportion of genes associated with PD encode proteins involved in the autophagy-lysosomal pathway. In this review, we highlight the evidence for the targeting of mitochondria by proteotoxic, redox and metabolic stress, and the role autophagic surveillance in maintenance of mitochondrial quality. Furthermore, we summarize the role of α-synuclein, leucine-rich repeat kinase 2, and tau in modulating mitochondrial function and autophagy. Among the stressors that can overwhelm the mitochondrial quality control mechanisms, we will discuss 4-hydroxynonenal and nitric oxide. The impact of autophagy is context depend and as such can have both beneficial and detrimental effects. Furthermore, we highlight the potential of targeting mitochondria and autophagic function as an integrated therapeutic strategy and the emerging contribution of the microbiome to PD susceptibility.

8 Review Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System. 2018

Andres, Daniela S / Darbin, Olivier. ·From the Science and Technology School, National University of San Martin, Buenos Aires, Argentina (DSA) · the Department of Neurology, University of South Alabama, Mobile, Ala. (OD) · and the Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Japan (OD). ·J Neuropsychiatry Clin Neurosci · Pubmed #29183233.

ABSTRACT: The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

9 Review Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. 2017

Obeso, J A / Stamelou, M / Goetz, C G / Poewe, W / Lang, A E / Weintraub, D / Burn, D / Halliday, G M / Bezard, E / Przedborski, S / Lehericy, S / Brooks, D J / Rothwell, J C / Hallett, M / DeLong, M R / Marras, C / Tanner, C M / Ross, G W / Langston, J W / Klein, C / Bonifati, V / Jankovic, J / Lozano, A M / Deuschl, G / Bergman, H / Tolosa, E / Rodriguez-Violante, M / Fahn, S / Postuma, R B / Berg, D / Marek, K / Standaert, D G / Surmeier, D J / Olanow, C W / Kordower, J H / Calabresi, P / Schapira, A H V / Stoessl, A J. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles, Madrid, Spain. · Universidad CEU San Pablo, Madrid, Spain. · CIBERNED, Madrid, Spain. · Department of Neurology, Philipps University, Marburg, Germany. · Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital and Attikon Hospital, University of Athens, Athens, Greece. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · Department of Medicine, University of Toronto, Toronto, Canada. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Corporal Michael J. Crescenz Veteran's Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Medical Sciences, Newcastle University, Newcastle, UK. · Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia. · School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney, Australia. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. · China Academy of Medical Sciences, Institute of Lab Animal Sciences, Beijing, China. · Departments of Neurology, Pathology, and Cell Biology, the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA. · Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA. · Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France. · Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Clinical Sciences Department, Newcastle University, Newcastle, UK. · Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark. · Human Neurophysiology, Sobell Department, UCL Institute of Neurology, London, UK. · Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. · Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Movement Disorders and Neuromodulation Center, Department of Neurology, University of California-San Francisco, San Francisco, California, USA. · Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA. · Parkinson's Institute, Sunnyvale, California, USA. · Institute of Neurogenetics, University of Luebeck, Luebeck, Germany. · Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Department of Neurology, Universitätsklinikum Schleswig-Holstein, Christian Albrechts University Kiel, Kiel, Germany. · Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Jerusalem, Israel. · Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel. · Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. · Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Medicine, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Barcelona, Spain. · Movement Disorders Clinic, Clinical Neurodegenerative Research Unit, Mexico City, Mexico. · Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada. · Klinik für Neurologie, UKSH, Campus Kiel, Christian-Albrechts-Universität, Kiel, Germany. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, Illinois, USA. · Neuroscience Graduate Program, Rush University Medical Center, Chicago, Illinois, USA. · Neurological Clinic, Department of Medicine, Hospital Santa Maria della Misericordia, University of Perugia, Perugia, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, Rome, Italy. · University Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, London, UK. · Pacific Parkinson's Research Centre, Division of Neurology & Djavadf Mowafaghian Centre for Brain Health, University of British Columbia, British Columbia, Canada. · Vancouver Coastal Health, Vancouver, British Columbia, Canada. ·Mov Disord · Pubmed #28887905.

ABSTRACT: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

10 Review Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease. 2017

West, Andrew B. ·Center for Neurodegeneration and Experimental Therapeutics, 1719 6th Ave. South, University of Alabama at Birmingham, Birmingham, AL 35294, United States of America. Electronic address: abwest@uab.edu. ·Exp Neurol · Pubmed #28764903.

ABSTRACT: In the translation of discoveries from the laboratory to the clinic, the track record in developing disease-modifying therapies in neurodegenerative disease is poor. A carefully designed development pipeline built from discoveries in both pre-clinical models and patient populations is necessary to optimize the chances for success. Genetic variation in the leucine-rich repeat kinase two gene (LRRK2) is linked to Parkinson disease (PD) susceptibility. Pathogenic mutations, particularly those in the LRRK2 GTPase (Roc) and COR domains, increase LRRK2 kinase activities in cells and tissues. In some PD models, small molecule LRRK2 kinase inhibitors that block these activities also provide neuroprotection. Herein, the genetic and biochemical evidence that supports the involvement of LRRK2 kinase activity in PD susceptibility is reviewed. Issues related to the definition of a therapeutic window for LRRK2 inhibition and the safety of chronic dosing are discussed. Finally, recommendations are given for a biomarker-guided initial entry of LRRK2 kinase inhibitors in PD patients. Four key areas must be considered for achieving neuroprotection with LRRK2 kinase inhibitors in PD: 1) identification of patient populations most likely to benefit from LRRK2 kinase inhibitors, 2) prioritization of superior LRRK2 small molecule inhibitors based on open disclosures of drug performance, 3) incorporation of biomarkers and empirical measures of LRRK2 kinase inhibition in clinical trials, and 4) utilization of appropriate efficacy measures guided in part by rigorous pre-clinical modeling. Meticulous and rational development decisions can potentially prevent incredibly costly errors and provide the best chances for LRRK2 inhibitors to slow the progression of PD.

11 Review C. elegans as a model system to accelerate discovery for Parkinson disease. 2017

Martinez, Bryan A / Caldwell, Kim A / Caldwell, Guy A. ·Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA. · Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA. Electronic address: gcaldwel@ua.edu. ·Curr Opin Genet Dev · Pubmed #28242493.

ABSTRACT: The nematode Caenorhabditis elegans possesses a wealth of opportunities to explore mechanisms which regulate metazoan complexity, basic cellular biology, and neuronal system attributes. Together, these provide a basis for tenable understanding of neurodegenerative disorders such as Parkinson disease (PD) through functional genomic analysis and pharmacological manipulation for the discovery of previously unknown genetic and environmental risk factors. The application of C. elegans has proven prescient in terms of the elucidation of functional effectors of cellular mechanisms underlying PD that translate to mammals. The current state of PD research using C. elegans encompasses defining obscure combinatorial interactions between genes or between genes and the environment, and continues to provide opportunities for the discovery of new therapeutic targets and disease-modifying drugs.

12 Review Biomarker-driven phenotyping in Parkinson's disease: A translational missing link in disease-modifying clinical trials. 2017

Espay, Alberto J / Schwarzschild, Michael A / Tanner, Caroline M / Fernandez, Hubert H / Simon, David K / Leverenz, James B / Merola, Aristide / Chen-Plotkin, Alice / Brundin, Patrik / Kauffman, Marcelo A / Erro, Roberto / Kieburtz, Karl / Woo, Daniel / Macklin, Eric A / Standaert, David G / Lang, Anthony E. ·Department of Neurology, UC Gardner Neuroscience Institute, Gardner Center for Parkinson's disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA. · MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Neurology, University of California-San Francisco and the Parkinson's Disease Research Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. · Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, USA. · Consultorio y Laboratorio de Neurogenética, Centro Universitario de Neurología "José María Ramos Mejía" y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA, and Programa de Medicina de Precision y Genomica Clinica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Pilar, Argentina. · Sobell department of Motor Neuroscience and Movement Disorders, University College London, Institute of Neurology, London, United Kingdom. · Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy. · Department of Neurology and CHET, University of Rochester Medical Center, Rochester, New York, USA. · Department of Neurology and Rehabilitation Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA. · Department of Medicine, Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA. · Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital and The Edmond J. Safra Program in PD, Toronto, Ontario, Canada, University of Toronto, Toronto, Ontario, Canada. ·Mov Disord · Pubmed #28233927.

ABSTRACT: Past clinical trials of putative neuroprotective therapies have targeted PD as a single pathogenic disease entity. From an Oslerian clinicopathological perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: A single-mechanism therapy can affect most of those sharing the classic pathological hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological, and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers), rather than clinical definitions, are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller, but well-defined, subsets of PD amenable to successful neuroprotection. © 2017 International Parkinson and Movement Disorder Society.

13 Review My Dad Can Beat Your Dad: Agonists, Antagonists, Partial Agonists, and Inverse Agonists. 2017

Kowalski, Peter C / Dowben, Jonathan S / Keltner, Norman L. ·Peter C. Kowalski, MD, is a Child, Adolescent, and Adult Psychiatrist at the Behavioral Health Center of Eastern Idaho Regional Medical Center, Idaho Falls, Idaho, USA. · Jonathan S. Dowben, MD, is a Staff Psychiatrist, Child and Family, Behavioral Health Service, Brooke Army Medical Center (BAMC), Fort Sam Houston, Texas, USA. · Norman L. Keltner, EdD, CRNP, is a Professor, School of Nursing (retired), University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Perspect Psychiatr Care · Pubmed #28090636.

ABSTRACT: -- No abstract --

14 Review Parkin and PINK1 functions in oxidative stress and neurodegeneration. 2017

Barodia, Sandeep K / Creed, Rose B / Goldberg, Matthew S. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL 35294, United States. · Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, AL 35294, United States. Electronic address: mattgoldberg@uab.edu. ·Brain Res Bull · Pubmed #28017782.

ABSTRACT: Loss-of-function mutations in the genes encoding Parkin and PINK1 are causally linked to autosomal recessive Parkinson's disease (PD). Parkin, an E3 ubiquitin ligase, and PINK1, a mitochondrial-targeted kinase, function together in a common pathway to remove dysfunctional mitochondria by autophagy. Presumably, deficiency for Parkin or PINK1 impairs mitochondrial autophagy and thereby increases oxidative stress due to the accumulation of dysfunctional mitochondria that release reactive oxygen species. Parkin and PINK1 likely have additional functions that may be relevant to the mechanisms by which mutations in these genes cause neurodegeneration, such as regulating inflammation, apoptosis, or dendritic morphogenesis. Here we briefly review what is known about functions of Parkin and PINK1 related to oxidative stress and neurodegeneration.

15 Review Effects of α-synuclein on axonal transport. 2017

Volpicelli-Daley, Laura A. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: lvolpicellidaley@uabmc.edu. ·Neurobiol Dis · Pubmed #27956085.

ABSTRACT: Lewy bodies and Lewy neurites composed primarily of α-synuclein characterize synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Despite decades of research on the impact of α-synuclein, little is known how abnormal inclusion made of this protein compromise neuronal function. Emerging evidence suggests that defects in axonal transport caused by aggregated α-synuclein contribute to neuronal dysfunction. These defects appear to occur well before the onset of neuronal death. Susceptible neurons in PD such as dopamine neurons with long elaborate axons may be particularly sensitive to abnormal axonal transport. Axonal transport is critical for delivery of signaling molecules to the soma responsible for neuronal differentiation and survival. In addition, axonal transport delivers degradative organelles such as endosomes and autophagosomes to lysosomes located in the soma to degrade damaged proteins and organelles. Identifying the molecular mechanisms by which axonal transport is impaired in PD and DLB may help identify novel therapeutic targets to enhance neuron survival and even possibly prevent disease progression. Here, we review the evidence that axonal transport is impaired in synucleinopathies, and describe potential mechanisms by which contribute to these defects.

16 Review A systematic review of the literature on disorders of sleep and wakefulness in Parkinson's disease from 2005 to 2015. 2017

Chahine, Lama M / Amara, Amy W / Videnovic, Aleksandar. ·Parkinson's Disease and Movement Disorders Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 330 S. 9th st, Philadelphia, PA 19107, USA. Electronic address: lamachahine@hotmail.com. · Division of Movement Disorders, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA. · Neurobiological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·Sleep Med Rev · Pubmed #27863901.

ABSTRACT: Sleep disorders are among the most common non-motor manifestations in Parkinson's disease (PD) and have a significant negative impact on quality of life. While sleep disorders in PD share most characteristics with those that occur in the general population, there are several considerations specific to this patient population regarding diagnosis, management, and implications. The available research on these disorders is expanding rapidly, but many questions remain unanswered. We thus conducted a systematic review of the literature published from 2005 to 2015 on the following disorders of sleep and wakefulness in PD: REM sleep behavior disorder, insomnia, nocturia, restless legs syndrome and periodic limb movements, sleep disordered breathing, excessive daytime sleepiness, and circadian rhythm disorders. We discuss the epidemiology, etiology, clinical implications, associated features, evaluation measures, and management of these disorders. The influence on sleep of medications used in the treatment of motor and non-motor symptoms of PD is detailed. Additionally, we suggest areas in need of further research.

17 Review How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson's disease? 2016

Volpicelli-Daley, Laura A / Kirik, Deniz / Stoyka, Lindsay E / Standaert, David G / Harms, Ashley S. ·From the Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama. volpicel@uab.edu. · Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, Lund, Sweden. · From the Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama. ·J Neurochem · Pubmed #27018978.

ABSTRACT: Animal models of Parkinson's disease (PD) are important for understanding the mechanisms of the disease and can contribute to developing and validating novel therapeutics. Ideally, these models should replicate the cardinal features of PD, such as progressive neurodegeneration of catecholaminergic neurons and motor defects. Many current PD models emphasize pathological forms of α-synuclein, based on findings that autosomal dominant mutations in α-synuclein and duplications/triplications of the SNCA gene cause PD. In addition, Lewy bodies and Lewy neurites, primarily composed of α-synuclein, represent the predominant pathological characteristics of PD. These inclusions have defined features, such as insolubility in non-ionic detergent, hyperphosphorylation, proteinase K sensitivity, a filamentous appearance by electron microscopy, and β-sheet structure. Furthermore, it has become clear that Lewy bodies and Lewy neurites are found throughout the peripheral and central nervous system, and could account not only for motor symptoms, but also for non-motor symptoms of the disease. The goal of this review is to describe two new α-synuclein-based models: the recombinant adeno-associated viral vector-α-synuclein model and the α-synuclein fibril model. An advantage of both models is that they do not require extensive crossbreeding of rodents transgenic for α-synuclein with other rodents transgenic for genes of interest to study the impact of such genes on PD-related pathology and phenotypes. In addition, abnormal α-synuclein can be expressed in brain regions relevant for disease. Here, we discuss the features of each model, how each model has contributed thus far to our understanding of PD, and the advantages and potential caveats of each model. This review describes two α-synuclein-based rodent models of Parkinson's disease: the rAAV-α-synuclein model and the α-synuclein fibril model. The key features of these models are described, and the extent to which they recapitulate features of PD, such as α-synuclein inclusion formation, loss of dopaminergic synapses in the striatum, motor defects, inflammation, and dopamine neuron death. This article is part of a special issue on Parkinson disease.

18 Review Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases. 2016

Irwin, Michael H / Moos, Walter H / Faller, Douglas V / Steliou, Kosta / Pinkert, Carl A. ·Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. · Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA. · SRI Biosciences, A Division of SRI International, Menlo Park, CA, USA. · Cancer Research Center, Boston University School of Medicine, Boston, MA, USA. · PhenoMatriX, Inc., Boston, MA, USA. · Department of Biological Sciences, College of Arts and Sciences, The University of Alabama, Tuscaloosa, AL, USA. ·Drug Dev Res · Pubmed #26899010.

ABSTRACT: Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.

19 Review Trophic factors for Parkinson's disease: To live or let die. 2015

Olanow, C Warren / Bartus, Raymond T / Volpicelli-Daley, Laura A / Kordower, Jeffrey H. ·Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA. · RTBioconsultants, Inc., San Diego, CA, USA. · University of Alabama at Birmingham, Birmingham, Alabama, USA. · Rush University Medical Center, Chicago, Illinois, USA. ·Mov Disord · Pubmed #26769457.

ABSTRACT: Trophic factors show great promise in laboratory studies as potential therapies for PD. However, multiple double-blind, clinical trials have failed to show benefits in comparison to a placebo control. This article will review the scientific rationale for testing trophic factors in PD, the results of the different clinical trials that have been performed to date, and the possible explanations for these failed outcomes. We will also consider future directions and the likelihood that trophic factors will become a viable therapy for patients with PD.

20 Review Role of α-synuclein in inducing innate and adaptive immunity in Parkinson disease. 2015

Allen Reish, Heather E / Standaert, David G. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Alabama, USA. ·J Parkinsons Dis · Pubmed #25588354.

ABSTRACT: Alpha-synuclein (α-syn) is central to the pathogenesis of Parkinson disease (PD). Gene duplications, triplications and point mutations in SNCA1, the gene encoding α-syn, cause autosomal dominant forms of PD. Aggregated and post-translationally modified forms of α-syn are present in Lewy bodies and Lewy neurites in both sporadic and familial PD, and recent work has emphasized the prion-like ability of aggregated α-syn to produce spreading pathology. Accumulation of abnormal forms of α-syn is a trigger for PD, but recent evidence suggests that much of the downstream neurodegeneration may result from inflammatory responses. Components of both the innate and adaptive immune systems are activated in PD, and influencing interactions between innate and adaptive immune components has been shown to modify the pathological process in animal models of PD. Understanding the relationship between α-syn and subsequent inflammation may reveal novel targets for neuroprotective interventions. In this review, we examine the role of α-syn and modified forms of this protein in the initiation of innate and adaptive immune responses.

21 Review M1 and M2 immune activation in Parkinson's Disease: Foe and ally? 2015

Moehle, M S / West, A B. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address: msmoehle@gmail.com. · Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, United States. ·Neuroscience · Pubmed #25463515.

ABSTRACT: Parkinson's Disease (PD) is a chronic and progressive neurodegenerative disorder of unknown etiology. Autopsy findings, genetics, retrospective studies, and molecular imaging all suggest a role for inflammation in the neurodegenerative process. However, relatively little is understood about the causes and implications of neuroinflammation in PD. Understanding how inflammation arises in PD, in particular the activation state of cells of the innate immune system, may provide an exciting opportunity for novel neuroprotective therapeutics. We analyze the evidence of immune system involvement in PD susceptibility, specifically in the context of M1 and M2 activation states. Tracking and modulating these activation states may provide new insights into both PD etiology and therapeutic strategies.

22 Review Ten years and counting: moving leucine-rich repeat kinase 2 inhibitors to the clinic. 2015

West, Andrew B. ·Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. ·Mov Disord · Pubmed #25448543.

ABSTRACT: The burden that Parkinson's disease (PD) exacts on the population continues to increase year after year. Though refinement of symptomatic treatments continues at a reasonable pace, no accepted therapies are available to slow or prevent disease progression. The leucine-rich repeat kinase 2 (LRRK2) gene was identified in PD genetic studies and offers new hope for novel therapeutic approaches. The evidence linking LRRK2 kinase activity to PD susceptibility is presented, as well as seminal discoveries relevant to the prosecution of LRRK2 kinase inhibition. Finally, suggestions are made for predictive preclinical modeling and successful first-in-human trials.

23 Review Mitophagy mechanisms and role in human diseases. 2014

Redmann, Matthew / Dodson, Matthew / Boyer-Guittaut, Michaël / Darley-Usmar, Victor / Zhang, Jianhua. ·Center for Free Radical Biology, University of Alabama at Birmingham, USA; Department of Pathology, University of Alabama at Birmingham, USA. · Université de Franche-Comté, Laboratoire de Biochimie, EA3922, SFR IBCT FED4234, Sciences et Techniques, 16 route de Gray, 25030 Besançon Cedex, France. · Center for Free Radical Biology, University of Alabama at Birmingham, USA; Department of Pathology, University of Alabama at Birmingham, USA; Department of Veterans Affairs, Birmingham VA Medical Center, AL 35294, USA. Electronic address: zhanja@uab.edu. ·Int J Biochem Cell Biol · Pubmed #24842106.

ABSTRACT: Mitophagy is a process of mitochondrial turnover through lysosomal mediated autophagy activities. This review will highlight recent studies that have identified mediators of mitophagy in response to starvation, loss of mitochondrial membrane potential or perturbation of mitochondrial integrity. Furthermore, we will review evidence of mitophagy dysfunction in various human diseases and discuss the potential for therapeutic interventions that target mitophagy processes.

24 Review MR anatomy of deep brain nuclei with special reference to specific diseases and deep brain stimulation localization. 2014

Telford, Ryan / Vattoth, Surjith. ·Department of Radiology, University of Alabama at Birmingham; Birmingham, AL, USA - rtelford@uabmc.edu. · Department of Radiology, University of Alabama at Birmingham; Birmingham, AL, USA. ·Neuroradiol J · Pubmed #24571832.

ABSTRACT: Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures.

25 Review Nonmotor symptoms in Parkinson's disease: expanding the view of Parkinson's disease beyond a pure motor, pure dopaminergic problem. 2013

Sung, Victor W / Nicholas, Anthony P. ·Department of Neurology, University of Alabama at Birmingham and Birmingham VA Medical Center, 1720 7th Avenue South, Birmingham, AL 35294, USA. vsung@uab.edu ·Neurol Clin · Pubmed #23931951.

ABSTRACT: Nonmotor symptoms (NMS) of Parkinson's disease (PD) are critical to identify and treat because of their impact on quality of life. Despite growing evidence of the importance of NMS on patients' quality of life, gaps remain in their recognition and treatment. The result is a need for increased information and understanding of specific NMS and the clinical approaches for their assessment and management in the context of PD as a whole. This article discusses the NMS of PD, their relationship to the pathologic basis of PD, and how NMS can be best managed.

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