Abstract: α-Synuclein is a neuronal protein originally identified in Alzheimer's disease (AD) amyloid plaques in 1993 and named non-Aβ component precursor (NACP) [92]. Later, the discovery of two missense mutations (G88C and G209A), which resulted in Ala30Pro (A30P) and Ala53Thr (A53T) substitutions, of the α-synuclein gene in certain autosomal-dominant early onset familial Parkinson's disease (PD) has greatly promoted the understanding of the role of α-synuclein in the pathogenesis of neurodegenerative diseases, such as PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) [5,6,51,75]. At present, it is widely accepted that α-synuclein may play a central role in several neurodegenerative…disorders because of the presence of insoluble α-synuclein as the major fibrillar component of inclusion bodies. From the cloning of the human α-synuclein cDNA in 1993 to the present, α-synuclein has been carefully documented in many aspects. In this article, we review the progress of studies on α-synuclein and its role inα-synuclein-related neurodegenerative diseases.
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Abstract: α-Synuclein is a major constituent of pathological intracellular inclusion bodies, a common feature of several neurodegenerative diseases. Two missense mutations in the α-synuclein gene have been identified in confirmed autosomal-dominant familial Parkinson's disease, which segregate with the illness. However, the physiological function of α-synuclein remains unknown. After biochemical investigations we have revealed tubulin to be an α-synuclein associated/binding protein. Here, we show that α-synuclein induces polymerization of purified tubulin into microtubules. Mutant forms of α-synuclein lose this potential. The binding site of α-synuclein to tubulin is identified, and co-localization of α-synuclein with microtubules is shown in cultured cells. To our…knowledge, this is the first demonstration of microtubule-polymerizing activity of α-synuclein. Now we can see a striking resemblance between α-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. The discovery of a physiological role for α-synuclein may provide a new dimension in researches into the mechanisms of α-synuclein-associated neurodegenerative diseases.
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