The role of Ser129 phosphorylation of α-synuclein in neurodegeneration of Parkinson’s disease: a review of in vivo models
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Hiroyasu Sato
Hiroyasu Sato graduated in medicine from Yamagata University in 2002. He was trained in internal medicine and neurology at the Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine. Dr. Sato is interested in neurodegenerative diseases, such as Parkinson’s disease. The focus of his research is the development of an animal model of Parkinson’s disease and exploring the pathogenesis of this disease.
Prof. Takeo Kato graduated from Yamagata University School of Medicine, Yamagata, Japan, in 1979. He studied internal medicine including neurology in Yamagata University Hospital, and then neuropathology in Montefiore Medical Center, New York, USA, from 1984 to 1986. He is now the professor and chairman of the Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, and the head of the Research Center for Metabolic and Degenerative Diseases, Yamagata University, Yamagata, Japan. He has a great interest in researches on Parkinson’s disease, amyotrophic lateral sclerosis, and normal pressure hydrocephalus.
Shigeki Arawaka graduated from Yamagata University School of Medicine at 1993. After completing a postdoctoral fellow at Centre for Research in Neurodegenerative Diseases, University of Toronto from 1999 to 2002, he is studying the toxic mechanism of α-synuclein in Parkinson’s disease using cellular and viral-mediated rodent models at Yamagata University Faculty of Medicine.
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.
About the authors
Hiroyasu Sato graduated in medicine from Yamagata University in 2002. He was trained in internal medicine and neurology at the Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine. Dr. Sato is interested in neurodegenerative diseases, such as Parkinson’s disease. The focus of his research is the development of an animal model of Parkinson’s disease and exploring the pathogenesis of this disease.
Prof. Takeo Kato graduated from Yamagata University School of Medicine, Yamagata, Japan, in 1979. He studied internal medicine including neurology in Yamagata University Hospital, and then neuropathology in Montefiore Medical Center, New York, USA, from 1984 to 1986. He is now the professor and chairman of the Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, and the head of the Research Center for Metabolic and Degenerative Diseases, Yamagata University, Yamagata, Japan. He has a great interest in researches on Parkinson’s disease, amyotrophic lateral sclerosis, and normal pressure hydrocephalus.
Shigeki Arawaka graduated from Yamagata University School of Medicine at 1993. After completing a postdoctoral fellow at Centre for Research in Neurodegenerative Diseases, University of Toronto from 1999 to 2002, he is studying the toxic mechanism of α-synuclein in Parkinson’s disease using cellular and viral-mediated rodent models at Yamagata University Faculty of Medicine.
©2013 by Walter de Gruyter Berlin Boston
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Artikel in diesem Heft
- Masthead
- Masthead
- The role of Ser129 phosphorylation of α-synuclein in neurodegeneration of Parkinson’s disease: a review of in vivo models
- The role of the subthalamic nucleus in cognition
- Physical exercise and Parkinson’s disease: influence on symptoms, disease course and prevention
- The role of serotonin in the antidyskinetic effects of deep brain stimulation: focus on antipsychotic-induced motor symptoms
- Imaging the structure of the human anxious brain: a review of findings from neuroscientific personality psychology
- 5-HT1A receptor as a key player in the brain 5-HT system
- Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders
- Effects of chronic stress on the auditory system and fear learning: an evolutionary approach
