title: Rabs, SNAREs and α-synuclein--membrane trafficking defects in synucleinopathies.
abstract: Neuronal dysfunctions and neurodegeneration are often associated with defects in membrane transport. Synucleinopathies are a diverse group of neurodegenerative disorders that share a common pathological feature--insoluble aggregates composed largely of the protein α-synuclein in certain populations of neurons and glia. The actual physiological function of the brain-enriched α-synuclein is still not particularly clear. What is obvious is that when the protein is present in pathologically high amounts, or in mutant forms with enhanced membrane association and oligomerization, it causes neuronal demise with manifestations of impaired neuronal traffic, heightened oxidative stress, mitochondrial degeneration and defects in lipid metabolism. α-synuclein's direct association with the activities of key components of the eukaryotic membrane traffic machinery, namely Rabs and the soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptors (SNAREs), has highlighted a key role for membrane transport defects in α-synuclein-mediated pathology. Here, we summarize and discuss recent findings in this regard, and their implications in the molecular aspects of synucleinopathy.
authors: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
authors: Christelle En Lin
authors: CE
authors: Chua
authors: Bor Luen
authors: BL
authors: Tang
mesh_terms: D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport / Q000235:genetics; D050600:SNARE Proteins / Q000235:genetics* / Q000502:physiology; D051844:alpha-Synuclein / Q000235:genetics* / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D050600:SNARE Proteins; D051844:alpha-Synuclein; D020691:rab GTP-Binding Proteins