title: Function of α-synuclein and PINK1 in Lewy body dementia (Review).
abstract: α-Synuclein (α-syn) is the major protein component of Lewy bodies, a key pathological characteristic of the degenerating brain. The misfolding and aggregation of α-syn is associated with both the idiopathic and familial forms of Parkinson's disease (PD) and Lewy body dementia (LBD). However, the function of α-syn is poorly understood, as it shows both neurotoxic and neuroprotective activities. Mutations in phosphatase and tensin homologue-induced putative kinase 1 (PINK1) also cause recessively inherited PD. Studies support the notion of neuroprotective roles for PINK1, as it protects cells from damage-induced mitochondrial dysfunction, oxidative stress and cell apoptosis. PINK1 plays an essential role in mitochondrial quality control and its homeostasis is maintained through mitochondrial stabilization. The α-syn aggregation is linked to various aspects of mitochondrial dysfunction and PINK1-related mitophagy. Determination of the molecular pathways that lead to α-syn oligomerization and further aggregation may be the basis for the successful design and development of treatments for these neurodegenerative diseases. The present review summarizes the function of PINK1 underlying α-syn aggregation and the mechanisms through which mitochondrial dysfunction plays a role in this process.
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Minami
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakanishi
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kitagishi
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ogura
mesh_terms: D000818:Animals; D004032:Diet; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D063306:Mitophagy / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase