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*

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*

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

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

Parkinson's disease is a multifactorial disorder with several genes linked to the familial types of the disease. ATP13A2 is one of those genes and encode for a transmembrane protein localized in lysosomes and late endosomes. Previous studies suggested the roles of this protein in lysosomal functions and cellular ion homeostasis. Here, we set out to investigate the role of ATP13A2 in lysosomal function and in metabolism of alpha-synuclein, another PD-linked protein whose accumulation is implicated in the pathogenesis. We generated non-sense mutations in both copies of ATP13A2 gene in SH-SY5Y human neuroblastoma cells. We examined lysosomal function of ATP13A2-/- cells by measuring the accumulation of lysosomal substrate proteins, such as p62 and polyubiquitinated proteins, induction of acidic compartments, and degradation of ectopically introduced dextran. None of these measures were altered by ATP13A2 deficiency. The steady-state levels of alpha-synuclein in cells or secretion of this protein were unaltered either in ATP13A2-/- compared to the normal cells. Therefore, the proposed roles of ATP13A2 in lysosomal functions may not be generalized and may depend on the cellular context. The ATP13A2-/- cells generated in the current study may provide a useful control for studies on the roles of PD genes in lysosomal functions.
alpha-Synuclein* ; Dextrans ; Endosomes ; Homeostasis ; Humans ; Lysosomes ; Metabolism* ; Neuroblastoma ; Parkinson Disease ; Polyubiquitin

Converging lines of evidence suggest that cell-to-cell transmission and the self-propagation of pathogenic amyloidogenic proteins play a central role in the initiation and the progression of several neurodegenerative disorders. This "prion-like" hypothesis has been recently reported for alpha-synuclein, a presynaptic protein implicated in the pathogenesis of Parkinson's disease (PD) and related disorders. This review summarizes recent findings on alpha-synuclein prion-like propagation, focusing on its transmission, seeding and degradation and discusses some key questions that remain to be explored. Understanding how alpha-synuclein exits cells and propagates from one brain region to another will lead to the development of new therapeutic strategies for the treatment of PD, aiming at slowing or stopping the disease progression.
alpha-Synuclein* ; Amyloidogenic Proteins ; Brain ; Disease Progression ; Neurodegenerative Diseases ; Parkinson Disease

Alpha-synuclein is a small neuronal protein that is closely associated with the etiology of Parkinson's disease. Mutations in and alterations in expression levels of alpha-synuclein cause autosomal dominant early onset heredity forms of Parkinson's disease, and sporadic Parkinson's disease is defined in part by the presence of Lewy bodies and Lewy neurites that are composed primarily of alpha-synuclein deposited in an aggregated amyloid fibril state. The normal function of alpha-synuclein is poorly understood, and the precise mechanisms by which it leads to toxicity and cell death are also unclear. Although alpha-synuclein is a highly soluble, cytoplasmic protein, it binds to a variety of cellular membranes of different properties and compositions. These interactions are considered critical for at least some normal functions of alpha-synuclein, and may well play critical roles in both the aggregation of the protein and its mechanisms of toxicity. Here we review the known features of alpha-synuclein membrane interactions in the context of both the putative functions of the protein and of its pathological roles in disease.
alpha-Synuclein* ; Amyloid ; Cell Death ; Cytoplasm ; Heredity ; Lewy Bodies ; Membranes* ; Neurites ; Neurons ; Parkinson Disease ; Synaptic Transmission