Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles from Singapore Republic
Based on 193 articles published since 2008
||||

These are the 193 published articles about Parkinson Disease that originated from Singapore Republic during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Editorial Linking statins and lipids in Parkinson's disease. 2017

Ng, Adeline S L / Tan, Eng-King. ·Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore. · Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore. · Duke-NUS Medical School, Singapore. ·Mov Disord · Pubmed #28556203.

ABSTRACT: -- No abstract --

2 Editorial Familial Parkinson's disease/parkinsonism. 2015

Tomiyama, Hiroyuki / Lesage, Suzanne / Tan, Eng-King / Jeon, Beom S. ·Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. · Sorbonne Universités, UPMC Université Paris 6 UMRS 1127, Inserm U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France. · Department of Neurology, Singapore General Hospital and Neuroscience & Behavioral Disorders Program, Duke-NUS Graduate Medical School, National Neuroscience Institute, Singapore. · Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea. ·Biomed Res Int · Pubmed #25961036.

ABSTRACT: -- No abstract --

3 Review Pathophysiological mechanisms linking F-box only protein 7 (FBXO7) and Parkinson's disease (PD). 2018

Zhou, Zhi Dong / Lee, Ji Chao Tristan / Tan, Eng King. ·Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore; Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Medical School, 8 College Road, 169857, Singapore. Electronic address: Zhidong_zhou@nni.com.sg. · Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore. Electronic address: tristan.lee.j.c@singhealth.com.sg. · Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore; Department of Neurology, Singapore General Hospital, Outram Road, 169608, Singapore; Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Medical School, 8 College Road, 169857, Singapore. Electronic address: Tan.eng.king@sgh.com.sg. ·Mutat Res · Pubmed #30454685.

ABSTRACT: Mutations of F-box only protein 7 (FBXO7) gene are associated with a severe form of autosomal recessive juvenile Parkinson's disease (PD) (PARK15) with clinical features of Parkinsonian-Pyramidal syndrome (PPS). FBXO7 is an adaptor protein in SCF

4 Review A New Hope for a Devastating Disease: Hydrogen Sulfide in Parkinson's Disease. 2018

Cao, Xu / Cao, Lei / Ding, Lei / Bian, Jin-Song. ·Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. · Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. phcbjs@nus.edu.sg. · Life Science Institute, National University of Singapore, Singapore, Singapore. phcbjs@nus.edu.sg. ·Mol Neurobiol · Pubmed #28536975.

ABSTRACT: Hydrogen sulfide (H

5 Review Genes and Nonmotor Symptoms in Parkinson's Disease. 2017

Lim, Ee-Wei / Tan, Eng-King. ·National Neuroscience Institute, Duke NUS Medical School, Singapore, Singapore. · National Neuroscience Institute, Duke NUS Medical School, Singapore, Singapore. Electronic address: tan.eng.king@singhealth.com.sg. ·Int Rev Neurobiol · Pubmed #28802918.

ABSTRACT: Published data on genetic risk factors of nonmotor symptoms (NMS) are relatively lacking since the first mutation responsible for Parkinson's disease (PD) being reported in 1996. This chapter provides a concise summary of genetic links to common individual NMS such as cognitive impairment, depression, psychosis, olfactory dysfunction, pain, and sleep disorders. Although some genetic variants such as apolipoprotein E and glucocerebrosidase demonstrate consistent links with certain NMS, it is difficult to draw definitive conclusions. A concerted effort involving standardized protocol in multiple centers and multiethnic groups will be useful to further investigate the association. With the help of high-throughput genomic techniques, more causative genes and novel genes will be discovered in the future and this will contribute further to the understanding of genetic susceptibility of NMS in PD.

6 Review Mood and neural correlates of excessive daytime sleepiness in Parkinson's disease. 2017

Wen, M-C / Chan, L L / Tan, L C S / Tan, E K. ·Department of Research, National Neuroscience Institute, Singapore, Singapore. · Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore. · Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. ·Acta Neurol Scand · Pubmed #28670700.

ABSTRACT: For patients with Parkinson's disease (PD), excessive daytime sleepiness (PD-EDS) is a debilitating non-motor symptom and may be affected by mood symptoms, especially depression and anxiety. Few neuroimaging works have attempted to identify the neural features of PD-EDS, but various findings were reported. The purpose of this study was to systematically review the literature on mood and neuroimaging correlates of PD-EDS. A MEDLINE, PubMed, EMBASE, and PsycInfo search for peer-reviewed original research articles on depression, anxiety, and neuroimaging in PD-EDS identified 26 studies on depression, nine on anxiety, and eight on neuroimaging. Half of the studies reported greater depression in PD-EDS-positive patients compared with PD-EDS-negative patients. There was a significantly positive correlation between depression and PD-EDS. Limited studies on anxiety in PD-EDS suggested a weak correlation between anxiety and EDS. For depression and anxiety, the effect sizes were medium when EDS was subjectively measured, but became small when EDS was objective measured. Current neuroimaging studies generally suggested diminished neural structural and functional features (eg, brain volume, white matter integrity as indicated by fractional anisotropy, and cerebral metabolism) in patients with PD-EDS. Future studies should apply objective and subjective measures of mood symptoms and EDS and improve the neuroimaging methodology via using multimodal techniques and whole-brain analysis to provide new clues on the mood and neural correlates of PD-EDS.

7 Review Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia. 2017

Kandiah, Nagaendran / Pai, Ming-Chyi / Senanarong, Vorapun / Looi, Irene / Ampil, Encarnita / Park, Kyung Won / Karanam, Ananda Krishna / Christopher, Stephen. ·Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital. · Duke-NUS, Graduate Medical School, Singapore. · Division of Behavioral Neurology, Department of Neurology. · Alzheimer's Disease Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. · Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. · Clinical Research Centre. · Department of Medicine, Hospital Seberang Jaya, Penang, Malaysia. · Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines. · Department of Neurology and Cognitive Disorders and Dementia Center, Institute of Convergence Bio-Health, Dong-A University College of Medicine, Busan, Republic of Korea. · Novartis Healthcare Private Limited, Hyderabad, India. · Novartis (Singapore) Pte. Ltd., Singapore. ·Clin Interv Aging · Pubmed #28458525.

ABSTRACT: Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

8 Review Targeting LRRK2 in Parkinson's disease: an update on recent developments. 2017

Chan, Sharon L / Tan, Eng-King. ·a Department of Neurology , National Neuroscience institute, Duke NUS Medical School , Singapore. ·Expert Opin Ther Targets · Pubmed #28443359.

ABSTRACT: INTRODUCTION: LRRK2 research has progressed significantly in recent years with more reports of LRRK2 interactors and the development of more specific and sophisticated LRRK2 kinase inhibitors. Identification of bone fide LRRK2 substrates will provide new therapeutic targets in LRRK2-linked Parkinson's disease (PD). Areas covered: This review aims to put current LRRK2 research into perspective. Beginning with recent LRRK2 mammalian models employed for in vivo validation of LRRK2 substrates, followed by updates on reported LRRK2 interactors and their inferred mechanisms. Finally an overview of commonly used LRRK2 kinase inhibitors will be depicted. Expert opinion: Identification of LRRK2 non-kinase functions suggests the possibility of alternative LRRK2 drug target sites and these should be further explored. Studies on the effects of LRRK2 kinase inhibition on its non-kinase function and its self-regulatory role will provide further insights on its pathophysiologic mechanisms. Development of robust measurements of LRRK2 inhibitor efficacy will be required. These would include identification of specific imaging ligands or direct biochemical assays that can accurately capture its intrinsic activity. Testing of new therapeutic drug targets in both LRRK2 carriers and non LRRK2-linked patients will be important since their phenotype is similar.

9 Review Rabs, Membrane Dynamics, and Parkinson's Disease. 2017

Tang, Bor Luen. ·Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597. · NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 117456. ·J Cell Physiol · Pubmed #27925204.

ABSTRACT: Genes encoding cellular membrane trafficking components, namely RAB7L1 and RAB39B, are more recently recognized factors associated with Parkinson's disease (PD). Encoded by a gene within the PARK16 locus, RAB7L1 interacts with Leucine-rich repeat kinase 2 (LRRK2) to act in intracellular transport processes that are likely important for neuronal survival and function. LRRK2 also directly phosphorylates a number of other Rab proteins. On the other hand, nonsense and missense mutations of the X-chromosome localized RAB39B were shown to underlie X-linked intellectual disability (ID) in male patients with early-onset PD. The cellular or neuronal functions of RAB39B are not yet known with certainty, but it has recently been shown to play a role in glutamate receptor trafficking. Importantly, RAB39B is also functionally connected to components for autophagy regulation, which affects α-synuclein processing and clearance. In this review, we discuss the association of Rabs with PD pathology, and potential etiological mechanisms whereby defects or deficiencies in certain Rab proteins could lead to PD susceptibility. J. Cell. Physiol. 232: 1626-1633, 2017. © 2016 Wiley Periodicals, Inc.

10 Review Sirtuins as modifiers of Parkinson's disease pathology. 2017

Tang, Bor Luen. ·Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore. ·J Neurosci Res · Pubmed #27402490.

ABSTRACT: Parkinson's disease (PD) is the most common movement disorder associated with the elderly which, other than symptomatic therapies, has no effective treatment or preventive measures. Sirtuins and their pharmacological activators/inhibitors have been associated with a range of neuroprotective effects, and a large body of work on sirtuins' influence on PD pathology has accumulated over the past decade. Here, evidence for sirtuins' activities as modifiers of PD pathology and how the mammalian sirtuin paralogues may have conflicting impacts on PD pathogenesis and disease progression is reviewed. The possible cellular and molecular mechanisms underlying sirtuin activities in PD are discussed in the light of current knowledge with reference to autophagy, mitochondrial homeostasis, and microtubule dynamics. © 2016 Wiley Periodicals, Inc.

11 Review Nutraceuticals in Parkinson's Disease. 2016

Hang, Liting / Basil, Adeline Henry / Lim, Kah-Leong. ·Neurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore. · Department of Physiology, National University of Singapore, Singapore, Singapore. · NUS Graduate School for Integrative Sciences and Engineering, Singapore, Singapore. · Neurodegeneration Research Laboratory, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore. phslkl@nus.edu.sg. · NUS Graduate School for Integrative Sciences and Engineering, Singapore, Singapore. phslkl@nus.edu.sg. · Duke-NUS Medical School, Singapore, Singapore. phslkl@nus.edu.sg. ·Neuromolecular Med · Pubmed #27147525.

ABSTRACT: Current pharmacological strategies for Parkinson's disease (PD), the most common neurological movement disorder worldwide, are predominantly symptom relieving and are often plagued with undesirable side effects after prolonged treatment. Despite this, they remain as the mainstay treatment for PD due to the lack of better alternatives. Nutraceuticals are compounds derived from natural food sources that have certain therapeutic value and the advent of which has opened doors to the use of alternative strategies to tackle neurodegenerative diseases such as PD. Notably, nutraceuticals are able to position themselves as a "safer" strategy due to the fact that they are naturally derived compounds, therefore possibly having less side effects. Significant efforts have been put into better comprehending the role of nutraceuticals in PD, and we will look at some of them in this review. Broadly speaking, these compounds execute their positive effects via modulating signalling pathways, inhibiting oxidative stress, inflammation and apoptosis, as well as regulating mitochondrial homoeostasis. Importantly, we will highlight how a component of green tea, epigallocatechin-3-gallate (EGCG), confers neuroprotection in PD via its ability to activate AMP kinase and articulate how its beneficial effects in PD are possibly due to enhancing mitochondrial quality control.

12 Review Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies. 2016

Wen, M-C / Chan, L L / Tan, L C S / Tan, E K. ·Department of Research, National Neuroscience Institute, Singapore, Singapore. · Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore. · Duke - National University of Singapore Graduate Medical School, Singapore, Singapore. · Department of Neurology, National Neuroscience Institute, Singapore. ·Eur J Neurol · Pubmed #27141858.

ABSTRACT: Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer-reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single-photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal-limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre-processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra-nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

13 Review Linking F-box protein 7 and parkin to neuronal degeneration in Parkinson's disease (PD). 2016

Zhou, Zhi Dong / Sathiyamoorthy, Sushmitha / Angeles, Dario C / Tan, Eng King. ·National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. zhidong_zhou@nni.com.sg. · Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore, 169857, Singapore. zhidong_zhou@nni.com.sg. · National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. · Department of Neurology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore. · National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. Tan.eng.king@sgh.com.sg. · Department of Neurology, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore. Tan.eng.king@sgh.com.sg. · Signature Research Program in Neuroscience and Behavioural Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore, 169857, Singapore. Tan.eng.king@sgh.com.sg. ·Mol Brain · Pubmed #27090516.

ABSTRACT: Mutations of F-box protein 7 (FBXO7) and Parkin, two proteins in ubiquitin-proteasome system (UPS), are both implicated in pathogenesis of dopamine (DA) neuron degeneration in Parkinson's disease (PD). Parkin is a HECT/RING hybrid ligase that physically receives ubiquitin on its catalytic centre and passes ubiquitin onto its substrates, whereas FBXO7 is an adaptor protein in Skp-Cullin-F-box (SCF) SCF(FBXO7) ubiquitin E3 ligase complex to recognize substrates and mediate substrates ubiquitination by SCF(FBXO7) E3 ligase. Here, we discuss the overlapping pathophysiologic mechanisms and clinical features linking Parkin and FBXO7 with autosomal recessive PD. Both proteins play an important role in neuroprotective mitophagy to clear away impaired mitochondria. Parkin can be recruited to impaired mitochondria whereas cellular stress can promote FBXO7 mitochondrial translocation. PD-linked FBXO7 can recruit Parkin into damaged mitochondria and facilitate its aggregation. WT FBXO7, but not PD-linked FBXO7 mutants can rescue DA neuron degeneration in Parkin null Drosophila. A better understanding of the common pathophysiologic mechanisms of these two proteins could unravel specific pathways for targeted therapy in PD.

14 Review Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges. 2016

Xiao, Bin / Ng, Huck Hui / Takahashi, Ryosuke / Tan, Eng-King. ·National Neuroscience Institute, Singapore, Singapore. · Genome Institute of Singapore, Singapore, Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore. · Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan. · National Neuroscience Institute, Singapore, Singapore Genome Institute of Singapore, Singapore, Singapore Department of Neurology, Singapore General Hospital, Singapore, Singapore Duke-NUS Graduate Medical School, Singapore, Singapore. ·J Neurol Neurosurg Psychiatry · Pubmed #26833176.

ABSTRACT: Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an 'in vivo' platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the 'ideal' neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced.

15 Review Revisiting the Medical Management of Parkinson's Disease: Levodopa versus Dopamine Agonist. 2016

Zhang, Jinglin / Tan, Louis Chew-Seng. ·Parkinson's Disease and Movement Disorder Center, Department of Neurology, National Neuroscience Institute, Republic of Singapore, USA National Parkinson Foundation International Center of Excellence, Singapore, 11 Jalan Tan Tock Seng, Singapore, 308433. louis_tan@nni.com.sg. ·Curr Neuropharmacol · Pubmed #26644151.

ABSTRACT: The optimal treatment strategy for Parkinson's disease has been debated for decades. The introduction of levodopa (LD) treatment is frequently delayed because of theoretical concerns about its toxicity or the risk of drug-induced motor complications. These concerns have resulted in "LD phobia" with clinicians selecting dopamine agonist (DA) over LD as initial therapy. More recently, a shift in the treatment approach towards initial LD use appears to be occurring. It is therefore necessary to review current evidence for the use of LD and DA. This review discusses the medical management of Parkinson's disease with regards to the use of LD versus DA. Pendulum swings in treatment strategies between LD-first and DA-first therapies should be avoided. A balanced perspective is needed as there is a place for both drugs in the management of PD.

16 Review Effectiveness of resistance training on muscle strength and physical function in people with Parkinson's disease: a systematic review and meta-analysis. 2016

Chung, Chloe Lau Ha / Thilarajah, Shamala / Tan, Dawn. ·Tan Tock Seng Hospital, Allied Health Division, Department of Physiotherapy, Singapore chloe.lh.chung@connect.polyu.hk. · Singapore General Hospital, Allied Health Division, Department of Physiotherapy, Singapore. · Singapore General Hospital, Allied Health Division, Department of Physiotherapy, Singapore Singapore Institute of Technology, Singapore. ·Clin Rehabil · Pubmed #25691582.

ABSTRACT: OBJECTIVES: To systematically review the evidence investigating the effectiveness of resistance training on strength and physical function in people with Parkinson's disease. DATA SOURCES: Seven electronic databases (COCHRANE, CINAHL, Medline ISI, Psycinfo, Scopus, Web of Science ISI and Embase) were systematically searched for full-text articles published in English between 1946 and November 2014 using relevant search terms. REVIEW METHODS: Only randomized controlled trials investigating the effects of resistance training on muscle strength and physical function in people with Parkinson's disease were considered. The PEDro scale was used to assess study quality. Studies with similar outcomes were pooled by calculating standardized mean differences (SMD) using fixed or random effects model, depending on study heterogeneity. RESULTS: Seven studies, comprising of 401 participants with early to advanced disease (Hoehn & Yahr stage 1 to 4), were included. The median quality score was 6/10. The meta-analyses demonstrated significant SMD in favour of resistance training compared to non-resistance training or no intervention controls for muscle strength (0.61; 95% CI, 0.35 to 0.87; P <0.001), balance (0.36; 95% CI, 0.08 to 0.64; P = 0.01) and parkinsonian motor symptoms (0.48; 95% CI, 0.21 to 0.75; P < 0.001) but not for gait, balance confidence and quality of life. CONCLUSION: This review demonstrates that moderate intensity progressive resistance training, 2-3 times per week over 8-10 weeks can result in significant strength, balance and motor symptoms gains in people with early to moderate Parkinson's disease.

17 Review microRNAs and Neurodegenerative Diseases. 2015

Qiu, Lifeng / Tan, Eng King / Zeng, Li. ·Neural Stem Cell Research Lab, Department of Research, National Neuroscience Institute, Singapore, 308433, Singapore. · Department of Neurology, National Neuroscience Institute, SGH Campus, Singapore, 169856, Singapore. · Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. · Neuroscience and Behavioral Disorders program, Duke-National University of Singapore, Graduate Medical School, Singapore, 169857, Singapore. · Neural Stem Cell Research Lab, Department of Research, National Neuroscience Institute, Singapore, 308433, Singapore. Li_ZENG@nni.com.sg. · Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. Li_ZENG@nni.com.sg. · Neuroscience and Behavioral Disorders program, Duke-National University of Singapore, Graduate Medical School, Singapore, 169857, Singapore. Li_ZENG@nni.com.sg. ·Adv Exp Med Biol · Pubmed #26663180.

ABSTRACT: microRNAs (miRNAs) are small, noncoding RNA molecules that through imperfect base-pairing with complementary sequences of target mRNA molecules, typically cleave target mRNA, causing subsequent degradation or translation inhibition. Although an increasing number of studies have identified misregulated miRNAs in the neurodegenerative diseases (NDDs) Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, which suggests that alterations in the miRNA regulatory pathway could contribute to disease pathogenesis, the molecular mechanisms underlying the pathological implications of misregulated miRNA expression and the regulation of the key genes involved in NDDs remain largely unknown. In this chapter, we provide evidence of the function and regulation of miRNAs and their association with the neurological events in NDDs. This will help improve our understanding of how miRNAs govern the biological functions of key pathogenic genes in these diseases, which potentially regulate several pathways involved in the progression of neurodegeneration. Additionally, given the growing interest in the therapeutic potential of miRNAs, we discuss current clinical challenges to developing miRNA-based therapeutics for NDDs.

18 Review Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection. 2015

Mukherjee, Uma A / Ong, Sang-Bing / Ong, Sang-Ging / Hausenloy, Derek J. ·The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK. · Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore. · Stanford Cardiovascular Institute, Stanford University School of Medicine, CA, USA. · The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, UK; Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore; The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, UK. Electronic address: derek.hausenloy@duke-nus.edu.sg. ·Pharmacol Ther · Pubmed #26481155.

ABSTRACT: Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death-through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection.

19 Review Asian perspectives on the recognition and management of levodopa 'wearing-off' in Parkinson's disease. 2015

Bhidayasiri, Roongroj / Hattori, Nobutaka / Jeon, Beomseok / Chen, Rou-Shayn / Lee, Moon Keen / Bajwa, Jawad A / Mok, Vincent C T / Zhang, Baorong / Syamsudin, Thamrin / Tan, Louis Chew Seng / Jamora, Roland Dominic G / Pisarnpong, Apichart / Poewe, Werner. ·a 1 Chulalongkorn Centre of Excellence for Parkinson's Disease & Related Disorders, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. · b 2 Juntendo University School of Medicine, Tokyo, Japan. · c 3 Seoul National University, Seoul, South Korea. · d 4 Chang Gung Memorial Hospital, Lingkou, Taiwan. · e 5 Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, 46150 Petaling Jaya, Selangor, Malaysia. · f 6 National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia. · g 7 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. · h 8 Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. · i 9 National Brain Centre Hospital, Jakarta, Indonesia. · j 10 National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore. · k 11 Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines. · l 12 Movement Disorder Service and Section of Neurology, Institute for Neurosciences, St. Luke's Medical Center-Quezon City and Global City, Philippines. · m 13 Department of Neurology, Bangkok Hospital, Bangkok, Thailand. · n 14 Innsbruck Medical University, Innsbruck, Austria. ·Expert Rev Neurother · Pubmed #26390066.

ABSTRACT: Most Parkinson's disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed 'wearing-off'. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson's disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.

20 Review Can clock drawing differentiate Alzheimer's disease from other dementias? 2015

Tan, Lynnette Pei Lin / Herrmann, Nathan / Mainland, Brian J / Shulman, Kenneth. ·Department of Psychiatry,Sunnybrook Health Sciences Centre,Canada;Department of Psychological Medicine,Tan Tock Seng Hospital,Singapore. · Division of Geriatric Psychiatry,Department of Psychiatry,Sunnybrook Health Sciences Centre,Canada;Department of Psychiatry,University of Toronto,Canada. · Department of Psychology,Ryerson University,Toronto,Canada. · Sunnybrook Health Sciences Centre,Canada;Department of Psychiatry,University of Toronto,Canada. ·Int Psychogeriatr · Pubmed #26138809.

ABSTRACT: BACKGROUND: Studies have shown the clock-drawing test (CDT) to be a useful screening test that differentiates between normal, elderly populations, and those diagnosed with dementia. However, the results of studies which have looked at the utility of the CDT to help differentiate Alzheimer's disease (AD) from other dementias have been conflicting. The purpose of this study was to explore the utility of the CDT in discriminating between patients with AD and other types of dementia. METHODS: A review was conducted using MEDLINE, PsycINFO, and Embase. Search terms included clock drawing or CLOX and dementia or Parkinson's Disease or AD or dementia with Lewy bodies (DLB) or vascular dementia (VaD). RESULTS: Twenty studies were included. In most of the studies, no significant differences were found in quantitative CDT scores between AD and VaD, DLB, and Parkinson's disease dementia (PDD) patients. However, frontotemporal dementia (FTD) patients consistently scored higher on the CDT than AD patients. Qualitative analyses of errors differentiated AD from other types of dementia. CONCLUSIONS: Overall, the CDT score may be useful in distinguishing between AD and FTD patients, but shows limited value in differentiating between AD and VaD, DLB, and PDD. Qualitative analysis of the type of CDT errors may be a useful adjunct in the differential diagnosis of the types of dementias.

21 Review Mitochondrial dysfunction and Parkinson disease: a Parkin-AMPK alliance in neuroprotection. 2015

Hang, Liting / Thundyil, John / Lim, Kah-Leong. ·Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore. · NUS Graduate School for Integrative Sciences and Engineering, Singapore. · Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School, Singapore. · Department of Physiology, National University of Singapore, Singapore. ·Ann N Y Acad Sci · Pubmed #26121488.

ABSTRACT: Although a subject of intense research, the etiology of Parkinson disease (PD) remains poorly understood. However, a wide range of studies conducted over the past few decades have collectively implicated aberrant mitochondrial homeostasis as a key contributor to the development of PD. Particularly strong support for this came from the recent demonstration that parkin, a familial PD-linked gene, is a critical regulator of mitochondrial quality control. Indeed, Parkin appears to be involved in all stages of the mitochondrial life cycle (i.e., from biogenesis to its exit from the cell (via mitophagy). Interestingly, the role of Parkin in the biogenesis and clearance of mitochondria is akin to that performed by the energy sensor AMP-activated protein kinase (AMPK), suggesting that the two proteins might act in a functionally converging manner to maintain the quality of cellular mitochondria. In this review, we discuss the contribution of mitochondrial dysfunction to PD pathogenesis and the role of Parkin and AMPK in preserving neuronal mitochondrial homeostasis. Alongside this, we will also articulate our thoughts on the potential alliance between Parkin and AMPK in offering neuroprotection through their ability to maintain energy balance in the brain.

22 Review Nonmotor symptoms in sporadic versus familial forms of Parkinson's disease. 2015

Chao, Yin Xia / Chew, Lai Mun / Deng, Xiao / Tan, Eng-King. ·National Neuroscience Institute, Singapore 308433, Singapore. ·Neurodegener Dis Manag · Pubmed #25894878.

ABSTRACT: Besides the classical motor symptoms, Parkinson's disease (PD) patients experience a wide range of nonmotor symptoms (NMS) throughout the disease course. However, due to the lack of recognition and understanding of the pathogenesis, NMS symptoms may be overlooked. Familial PD is a well-defined group that can provide a good model to investigate the mechanisms for both motor and NMS in PD. Some studies suggest that the frequency of NMS is not different between genetic and sporadic form of PD while others suggest that specific domains (such as neuropsychiatric symptoms) are more common in the genetic form. Early recognition of NMS may facilitate early diagnosis and monitoring of both sporadic and genetic PD.

23 Review Deciphering the function and regulation of microRNAs in Alzheimer's disease and Parkinson's disease. 2014

Qiu, Lifeng / Zhang, Wei / Tan, Eng King / Zeng, Li. ·Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute , 308433, Singapore. ·ACS Chem Neurosci · Pubmed #25210999.

ABSTRACT: MicroRNAs (miRNAs) are single stranded, noncoding RNA molecules that are encoded by eukaryotic nuclear DNA. miRNAs function through imperfect base-pairing with complementary sequences of target mRNA molecules, which is typically via the cleavage of target mRNA with transcriptional repression or translational degradation. An increasing number of studies identified dysregulation of miRNAs in neurodegenerative disease and suggest that alterations in the miRNA regulatory pathway could contribute to the disease pathogenesis. However, molecular mechanisms underlying the pathological implications of dysregulated miRNA expression and regulation of the key genes that are involved in neurodegenerative diseases remain largely unknown. Here, we review the evidence for the functional role of dysregulated miRNAs involved in disease pathogenesis, as well as how miRNAs govern neuronal functions either upstream or downstream of target genes that are disease pathogenic factors. Furthermore, we review the cellular feedback regulation between miRNAs and target genes in neurodegenerative diseases, with a focus on Alzheimer's disease and Parkinson's disease.

24 Review Evidence of inflammatory system involvement in Parkinson's disease. 2014

Chao, Yinxia / Wong, Siew Cheng / Tan, Eng King. ·National Neuroscience Institute, Singapore 308433 ; Duke-National University of Singapore Graduate Medical School, Singapore 169857. · Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648 ; Department of Microbiology, National University of Singapore, Singapore 117545. · National Neuroscience Institute, Singapore 308433 ; Duke-National University of Singapore Graduate Medical School, Singapore 169857 ; Department of Neurology, Singapore General Hospital, Singapore 169608 ; Department of Neurology, National Neuroscience Institute (SGH Campus), 20 College Road, Academia Level 4, Singapore 169856. ·Biomed Res Int · Pubmed #25050341.

ABSTRACT: Parkinson's disease (PD) is a chronic neurodegenerative disease underpinned by both genetic and environmental etiologic factors. Recent findings suggest that inflammation may be a pathogenic factor in the onset and progression of both familial and sporadic PD. Understanding the precise role of inflammatory factors in PD will likely lead to understanding of how the disease arises. In vivo evidence for inflammation in PD includes dysregulated molecular mediators such as cytokines, complement system and its receptors, resident microglial activation, peripheral immune cells invasion, and altered composition and phenotype of peripheral immune cells. The growing awareness of these factors has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Influences of ageing and differential exposure to environmental agents suggest potential host-pathogen specific pathophysiologic factors. There is a clear need for research to further unravel the pathophysiologic role of immunity in PD, with the potential of developing new therapeutic targets for this debilitating condition.

25 Review Genetic testing of LRRK2 in Parkinson's disease: is there a clinical role? 2014

Buhat, Donna Mae Lyn / Tan, Eng-King. ·Department of Neurology, National Neuroscience Institute, Singapore. ·Parkinsonism Relat Disord · Pubmed #24262189.

ABSTRACT: Genetic testing has played an important role for the diagnosis of many rare monogenic disorders. However, the role and limitations of genetic testing have generated considerable debate in the medical community. In recent years, the identification of several monogenic genes in Parkinson's disease (PD), a common neurodegenerative disorder, has led to calls for genetic testing guidelines for this disorder. Genetic testing of LRRK2 provides an excellent platform to highlight some of the pertinent issues (generic and specific) related to genetic testing in PD. The identification of a common recurrent mutation (G2019S) worldwide provides an opportunity for developing guidelines that are applicable internationally. However, the incomplete penetrance of the mutation and the lack of clarity of the pathogenicity of many other reported LRRK2 mutations call for cautious implementation of genetic testing programs. The clinical utility of genetic testing is compounded by easy accessibility of Direct to Consumer genetic services and the relative lack of regulation on reliability of service providers in internet advertisements. Based on current literature, genetic testing of LRRK2 (particularly for G2019S) certainly has a clinical role, though it is applicable primarily in select scenarios and in certain at-risk populations.

Next