The third exon of the  synuclein gene from a normal person and two Vietnamese persons with Prkinson’s disease was subcloned and sequenced. It was shown that in all cases there are two additional bases in the positions of C461 and T511. That is quite different from the sequence with DDBJ/Genbank accession number U46898. Besides, a mutation T543G was revealed in one Parkinson’s disease patien. All mentioned changes were located outside the region coding for third exon (G401-G442).
alpha-Synuclein ; Parkinson Disease

No abstract available.
alpha-Synuclein ; Colon ; Parkinson Disease

Parkinson's Disease (PD) is a complex and multifactorial disorder of both idiopathic and genetic origin. Thus far, more than 20 genes have been linked to familial forms of PD. Two of these genes encode for ATP13A2 and alpha-synuclein (asyn), proteins that seem to be members of a common network in both physiological and disease conditions. Thus, two different hypotheses have emerged supporting a role of ATP13A2 and asyn in metal homeostasis or in autophagy. Interestingly, an appealing theory might combine these two cellular pathways. Here we review the novel findings in the interaction between these two proteins and debate the exciting roads still ahead.
alpha-Synuclein* ; Autophagy* ; Homeostasis ; Parkinson Disease

Humans ; alpha-Synuclein/genetics* ; Parkinson Disease/pathology*

Here the author reviews the clinical and pathologic characteristics of dementia with Lewy bodies (DLB). DLB took many years to crystallize into a recognizable clinico-pathologic entity. Based on sensitive immunostaining technique, DLB is now considered the second most commonest cause of neurodegenerative dementia in the elderly. It is part of the range of clinical presentations that share a neuritic pathology based on abnormal aggregation of the synaptic protein alpha-synuclein. Lewy body pathology is found from the brainstem to the cortex and, in many cases, associated with concurrent Alzheimer' disease pathology. A recent international consortium on DLB has resulted in revised criteria for the clinical and pathological diagnosis of DLB incorporating new information about the clinical features and improved methods for their assessment. Neuropathologic diagnosis now assigns a weight to both alpha-synuclein and Alzheimer tangle pathology. Accurate identification of patients is important because they have specific symptoms, impairments, and functional disabilities that differ from those of other dementing illness including Alzheimer's disease.
Aged ; alpha-Synuclein ; Alzheimer Disease ; Brain Stem ; Dementia* ; Diagnosis ; Humans ; Lewy Bodies* ; Pathology

No abstract available.
Adult ; Cornea/*metabolism ; Fluorescent Antibody Technique, Indirect ; Humans ; Microscopy, Fluorescence ; Middle Aged ; alpha-Synuclein/*metabolism

Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy.
alpha-Synuclein ; Alzheimer Disease ; Dopaminergic Neurons ; Lewy Bodies ; Neurodegenerative Diseases ; Parkinson Disease*

Parkinson's disease (PD) and related Lewy body diseases are characterized by deposition of alpha-synuclein aggregates in both the central nervous system and peripheral nervous system. Synucleinopathy lesions spread to larger brain areas as the disease progresses, and prion-like cell-to-cell transmission of aggregated alpha-synuclein is thought to be the underlying mechanism for this pathological spreading. LRRK2 is another protein linked to the pathogenesis of PD, and its presence in Lewy bodies has attracted much attention as to whether LRRK2 and alpha-synuclein interplay during the pathogenesis of PD. However, the relationship between these two crucial proteins still remains unclear. In this review article, we will discuss the current state of knowledge in terms of how these proteins cause the disease and provide the hypothetical mechanisms by which LRRK2 might modify the generation and progression of synucleinopathy.
alpha-Synuclein ; Brain ; Central Nervous System ; Lewy Bodies ; Parkinson Disease* ; Peripheral Nervous System

During recent years, there has been remarkable progress with respect to the identification of molecular mechanisms and underlying pathology of neurodegenerative dementias. The latest evidence indicates that a common cause and pathological mechanism of diverse neurodegenerative dementias can be found in the increased production, misfolding, aggregation, and accumulation of specific proteins such as beta-amyloid, tau protein, alpha-synuclein, prion protein, polyglutamine, transactive response DNA-binding protein (TARDBP or TDP-43), or fused in sarcoma (FUS). The conformational variants of these proteins range from small oligomers to the characteristic pathologic inclusions. However, it is noteworthy that a certain pathology can be a hallmark of a certain dementia, but there is a substantial overlap between different pathologies and different types of dementias. In this review, molecular mechanisms and pathologies of different neurodegenerative dementias will be summarized from the perspective of proteins rather than from the viewpoint of individual dementias. We will also review recent evidence surrounding these protein misfolding disorders, the role of toxic oligomers, cell-to-cell transmission, and the links between the misfolded proteins, along with the general therapeutic strategies for the protein misfolding disorders.
alpha-Synuclein ; Dementia ; Neurodegenerative Diseases ; Peptides ; Proteins ; Proteostasis Deficiencies ; Sarcoma ; tau Proteins

BACKGROUND AND PURPOSE: The detection of alpha-synuclein in the body fluids of patients with synucleinopathy has yielded promising but inconclusive results, in part because of conformational changes of alpha-synuclein in response to environmental conditions. The aim of this study was to determine the feasibility of using alpha-synuclein as a biological marker for Parkinson's disease (PD). METHODS: Twenty-three drug-naive patients with PD (age 62.4+/-12.7 years, mean+/-SD; 11 males) and 29 age- and sex-matched neurologic control subjects (age 60.1+/-16.2 years; 16 males) were recruited. The levels of oligomeric and total alpha-synuclein in the cerebrospinal fluid (CSF) and plasma were measured using two simultaneous enzyme-linked immunosorbent assays. RESULTS: The level of alpha-synuclein oligomer in the CSF of PD patients was significantly higher in PD patients than in neurological controls, but other findings (plasma alpha-synuclein oligomer and total alpha-synuclein in CSF and plasma) did not differ significantly between the two groups. When the control subjects were divided into a symptomatic control group (11 patients who complained of parkinsonian symptoms and were diagnosed with hydrocephalus and drug-induced or vascular parkinsonism) and a neurologic control group (10 normal subjects and 8 patients with diabetic ophthalmoplegia), the level of alpha-synuclein oligomer in the CSF was still significantly higher in PD patients than in both of the control subgroups. CONCLUSIONS: These findings provide further evidence for a pathogenic role of the alpha-synuclein oligomer and suggest that CSF levels of alpha-synuclein oligomer can be a reliable marker for PD.
alpha-Synuclein ; Biomarkers ; Body Fluids ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hydrocephalus ; Parkinson Disease ; Plasma