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Cell replacement for Parkinson's disease:advances and challenges

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Neural Regeneration Research 2023年第12期18卷 2693-2694页

作者： Bin Xiao eng-king tan Department of Neurology National Neuroscience InstituteSingapore Neuroscience and Behavioral Disorders Program Duke-NUS Medical SchoolSingapore

Parkinson's disease(PD), characterized by the loss of dopaminergic(DA) neurons in the substantia nigra pars compacta(SNpc) of the midbrain, is a prototype neurological disease that is suitable for cellular replacement therapy. Levodopa has been utilized to replace the insufficient dopamine released by degenerating DA neurons since the 1960s and it remains the cornerstone of PD treatment. However, as the disease progresses.

关键词： dopamine corners replace

Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao Joshua Kuruvilla eng-king tan Department of Neurology National Neuroscience InstituteSingaporeSingapore Neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore Neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune *** et *** Chen et *** provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson’s disease in Drosophila

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Translational Neurodegeneration 2022年第1期11卷 262-279页

作者： Wei Liu Kah-Leong Lim eng-king tan School of Plant Protection Anhui Province Key Laboratory of Crop Integrated Pest ManagementAnhui Province Engineering Laboratory for Green Pesticide Development and ApplicationAnhui Agricultural UniversityHefei 230036China Department of Neurology National Neuroscience InstituteSingapore 308433Singapore Department of Research National Neuroscience InstituteSingaporeSingapore Research Lee Kong Chian School of Medi-cineSingaporeSingapore Neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingapore 169857Singapore.

Background:Aberrant aggregation ofα-synuclein(α-syn)is a key pathological feature of Parkinson’s disease(PD),but the precise role of intestinalα-syn in the progression of PD is *** a number of genetic Drosophila models of PD,α-syn was frequently ectopically expressed in the neural system to investigate the ***:We investigated the potential role of intestinalα-syn in PD pathogenesis using a Drosophila ***α-syn was overexpressed in Drosophila guts,and life span,survival,immunofluorescence and climbing were ***,Western blotting and reactive oxygen species(ROS)staining were performed to assess the effects of intestinalα-syn on intestinal ***‐throughput RNA and 16S rRNA gene sequencing,quantitative RT‐PCR,immunofluorescence,and ROS staining were performed to determine the underlying molecular ***:We found that the intestinalα-syn alone recapitulated many phenotypic and pathological features of PD,including impaired life span,loss of dopaminergic neurons,and progressive motor *** intestine-derivedα-syn disrupted intestinal homeostasis and accelerated the onset of intestinal ***,intestinal expression ofα-syn induced dysbiosis,while microbiome depletion was efficient to restore intestinal homeostasis and ameliorate the progression of ***α-syn triggered ROS,and eventually led to the activation of the dual oxidase(DUOX)-ROS-Jun N-terminal Kinase(JNK)*** addition,α-syn from both the gut and the brain synergized to accelerate the progression of ***:The intestinal expression ofα-syn recapitulates many phenotypic and pathologic features of PD,and induces dysbiosis that aggravates the pathology through the DUOX-ROS-JNK pathway in *** findings provide new insights into the role of intestinalα-syn in PD pathophysiology.

关键词： Intestine α-Synuclein Parkinson’s disease Microbiome

Linking restless legs syndrome with Parkinson’s disease:clinical,imaging and genetic evidence

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Translational Neurodegeneration 2012年第1期1卷 30-35页

作者： Tasneem Peeraully eng-king tan Department of Neurology Singapore General HospitalOutram RoadSingapore 169608Republic of Singapore

Restless legs syndrome(RLS)and Parkinson’s disease(PD)are both common neurological *** has been much debate over whether an etiological link between these two diseases exists and whether they share a common *** pointing towards a link includes response to dopaminergic agents in PD and RLS,suggestive of underlying dopamine dysfunction in both *** extrastriatal dopaminergic system,in particular altered spinal dopaminergic modulation,may be variably involved in PD patients with RLS *** addition,there is now evidence that the nigrostriatal system,primarily involved in PD,is also affected in ***,an association of RLS with the parkin mutation has been *** prevalence of RLS has also been reported to be increased in other disorders of dopamine ***,clinical association studies and functional imaging have produced mixed *** accounts of emergence of RLS and improvement in RLS symptoms after deep brain stimulation(DBS)also contribute to the uncertainty surrounding the *** the strongest arguments against a common pathophysiology is the role of iron in RLS and *** elevated iron levels in the substantia nigra contribute to oxidative stress in PD,RLS is a disorder of relative iron deficiency,with symptoms responding to replacement *** ultrasonography studies have suggested that,despite overlapping clinical features,the mechanisms underlying idiopathic RLS and RLS associated with PD may *** this review,we provide a concise summary of the clinical,imaging and genetic evidence exploring the link between RLS and PD.

关键词： Parkinson’s disease Restless-legs syndrome Pathophysiology Dopaminergic dysfunction

Mild cognitive impairment in Parkinson’s disease:a distinct clinical entity?

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Translational Neurodegeneration 2017年第1期6卷 225-231页

作者： Ming-Ching Wen Ling Ling Chan Louis C.S.tan eng king tan Department of Research National Neuroscience InstituteSingaporeSingapore Department of Neurology National Neuroscience Institute11 Jalan Tan Tock SengSingapore 308433Singapore Department of Diagnostic Radiology Singapore General HospitalSingaporeSingapore Duke-NUS Medical School SingaporeSingapore

Background:Mild cognitive impairment in Parkinson’s disease(PD-MCI)is a common clinical *** its pathology and clinical features is important for early intervention before the onset of *** the past,variable definitions and differences in neuropsychological batteries generated divergent results of the affected cognitive *** body:The introduction of PD-MCI criteria by the Movement Disorders Society(MDS)Task Force provides a more uniform system for defining and measuring PD-MCI and may improve the validity of future ***-MCI is likely to be heterogeneous since it can coexist with Alzheimer’s disease and/or Lewy body pathologies in *** of neuropsychiatric disturbances,such as depression,anxiety and apathy,are associated with PD with or without *** addition,cognitive reserve formed by patients’unique life experiences may influence the outward cognitive performance despite the presence of the aforementioned pathogeneses and hence alter the diagnosis of ***:The overlap of cognitive impairment across different neurodegenerative diseases suggests that PD-MCI is likely to result from a mixture of complex pathophysiologies,rather than being a distinct pathologic *** MCI from other organic symptoms in PD would facilitate novel therapeutic strategies.

关键词： Mild cognitive impairment Parkinson’s disease Alzheimer disease Lewy body Neuropsychiatric comorbidities Cognitive reserve

Role of dopamine in the pathophysiology of Parkinson’s disease

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Translational Neurodegeneration 2023年第1期12卷 281-295页

作者： Zhi Dong Zhou Ling Xiao Yi Dennis Qing Wang Tit Meng Lim eng king tan National Neuroscience Institute of Singapore 11 Jalan Tan Tock SengSingapore 308433Singapore Department of Neurology Singapore General HospitalOutram RoadSingapore 169608Singapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore8 College RoadSingapore 169857Singapore Department of Neurology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Department of Biological Science National University of SingaporeSingapore 119077Singapore

A pathological feature of Parkinson’s disease(PD)is the progressive loss of dopaminergic neurons and decreased dopamine(DA)content in the substantia nigra pars compacta in PD *** is the neurotransmitter of dopaminergic *** evidence suggests that DA interacts with environmental and genetic factors to contribute to PD *** of DA synthesis,storage,transportation and metabolism have been shown to promote neurodegeneration of dopaminergic neurons in various PD *** is unstable and can undergo oxidation and metabolism to produce multiple reactive and toxic by-products,including reactive oxygen species,DA quinones,and 3,*** we summarize and highlight recent discoveries on DA-linked pathophysiologic pathways,and discuss the potential protective and therapeutic strategies to mitigate the complications associated with DA.

关键词： Dopamine Dopamine quinones 3,4-Dihydroxyphenylacetaldehyde Neurodegeneration Pathogenesis Parkinson’s disease Reactive oxygen species Therapeutic strategies

Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease

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Translational Neurodegeneration 2019年第1期8卷 63-76页

作者： Zhi Dong Zhou Thevapriya Selvaratnam Ji Chao Tristan Lee Yin Xia Chao eng-king tan Department of Research National Neuroscience Institute11 Jalan Tan Tock SengSingapore 308433Singapore Department of Neurology Singapore General HospitalOutram RoadSingapore 169608Singapore Signature Research Program in Neuroscience and Behavioural Disorders Duke-NUS Medical School Singapore8 College RoadSingaporeSingapore

Parkinson’s disease(PD)is the most common neurodegenerative movement disorder,which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain *** detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear,and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in ***,the formation ofα-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD,possibly stemming from the consequence of protein misfolding and dysfunctional *** is the mechanism for maintaining protein homeostasis via modulation of protein translation,enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and *** protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes,leading to pathological protein aggregation and neurodegeneration in *** recent years,multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been *** potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

关键词： Molecular targets Neuron degeneration Parkinson’s disease Protein aggregation Protein translation Proteostasis

Symbiotic bacteria attenuate Drosophila oviposition repellence to alkaline through acidification

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Insect Science 2021年第2期28卷 403-414页

作者： Wei Liu Jie Wang Hong-Yu Zhang Ying-Chun Yang Ru-Xue Kang Peng Bai Hui Fu Li-Rong Chen Yan-Ping Gao eng king tan Department of Medical Laboratory Science Fenyang CollegeShanxi Medical UniversityShanxiChina Department of Neurology National Neuroscience InstituteSingapore General Hospital CampusSingapore Department of Basic Medical Fenyang CollegeShanxi Medical UniversityShanxiChina

Metazoans harbor a wealth of symbionts that are ever-changing the environment by taking up resources and/or excreting *** such common environmental modification is a change in *** wisdom holds that symbionts facilitate the survival and production of their hosts in the wild,but this notion lacks empirical ***,we report that symbiotic bacteria in the genus Enterococcus attenuate the oviposition avoidance of alkaline environments in *** studied the effects of alkalinity on oviposition preference for the first time,and found that flies are robustly disinclined to oviposit on alkali-containing *** innate repulsion to alkaline environments is explained,in part,by the fact that alkalinity compromises the health and lifespan of both offspring and parent *** dramatically diminished or even completely reversed the ovipositional avoidance of alkalinity in ***,Enterococcus generate abundant lactate during fermentation,which neutralizes the residual alkali in an egg-laying *** conclusion,Enterococcus protects Drosophila from alkali stress by acidifying the ovipositional substrate,and ultimately improves the fitness of the Drosophila *** results demonstrate that symbionts are profound factors in the Drosophila ovipositional decision,and extend our understanding of the intimate interactions between Drosophila and their symbionts.

关键词： acidification alkaline Drosophila,Enterococcus fitness oviposition

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帕金森病合并腿不宁的临床特点

帕金森病合并腿不宁的临床特点