title: The role of Ser129 phosphorylation of α-synuclein in neurodegeneration of Parkinson's disease: a review of in vivo models.
abstract: Parkinson's disease is the most common neurodegenerative movement disorder. The motor impairments of Parkinson's disease are caused by the loss of dopaminergic neurons in the substantia nigra and associated with the appearance of fibrillar aggregates of α-synuclein (α-syn) called Lewy bodies. Approximately 90% of α-syn deposited in Lewy bodies is phosphorylated at serine 129 (Ser129). In contrast, only 4% or less of total α-syn is phosphorylated at this residue in the normal brain. This suggests that the accumulation of Ser129-phosphorylated α-syn leads to the formation of Lewy bodies and dopaminergic neurodegeneration in Parkinson's disease. Our laboratory and others have performed experiments using in vivo models of Parkinson's disease to elucidate the role of increased Ser129 phosphorylation in α-syn neurotoxicity. However, there has been a lack of consistency among these models. In this review, we summarize the main findings regarding the relationship between Ser129 phosphorylation and α-syn neurotoxicity, and examine the differences among models. We further discuss the role of Ser129 phosphorylation in α-syn aggregation and the future directions to test the potential of Ser129 phosphorylation as a therapeutic target for slowing the progression of Parkinson's disease.
authors: Department of Neurology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Hiroyasu
authors: H
authors: Sato
authors: Takeo
authors: T
authors: Kato
authors: Shigeki
authors: S
authors: Arawaka
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D012694:Serine