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*

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

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

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