| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| 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.
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