Elucidation of mTOR-mediated autophagy common to the development of neuropsychiatric lesions and pigmental disorders

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461690
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Osaka University
• Principal Investigator: Mari Kaneda 大阪大学, 医学系研究科, 講師 (70397644)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: mTORC1 / オートファジー / 白斑 / 精神神経症状 / 結節性硬化症 / 色素細胞

Outline of Final Research Achievements

The aim of this study is to elucidate the association of mTORC1 and autophagy in neuropsychiatric disorders and pigment abnormality. Tuberous sclerosis complex (TSC) shows many neuronal symptoms and skin manifestations by the constitutive activation of mTORC1. mTORC1 negatively regulates autophagy, but impaired autophagy may cause neuropsychiatric disorders. However, the TSC-associated pathogenesis of hypopigmented macules remains to be elucidated. Here, we discovered that melanocyte autophagy was accelerated in skin of TSC patients with hypopigmented macules. When TSC2 was silenced in cultured human primary epidermal melanocytes, decreased pigmentation and increased LC3-II expression were observed. SiRNA-mediated silencing of the essential autophagy gene ATG7 increased pigmentation. TSC2 silencing-associated depigmentation was reversed by autophagy induction. Together, these results demonstrate that the impaired autophagy in melanocytes may contribute to hypopigmented macules in TSC.

Free Research Field

皮膚科