Elucidation of mTOR-mediated autophagy common to the development of neuropsychiatric lesions and pigmental disorders
| Project/Area Number |
25461690
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Osaka University |
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Principal Investigator |
Mari Kaneda 大阪大学, 医学系研究科, 講師 (70397644)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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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| 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 / 色素異常 / メラノソームの形成 / メラノサイト / 中枢神経症状 / 自閉症 / mTOR / 精神神経病変 / 結節性硬化症（TSC) / ｍTORC1 / メラニン産生過程 / 電子顕微鏡 |
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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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Report
(5 results)
Research Products
(75 results)
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[Journal Article] Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum.2017
Author(s)
Iwanaga A, Okubo Y, Yozaki M, Koike Y, Kuwatsuka Y, Tomimura S, Yamamoto Y, Tamura H, Ikeda S, Maemura K, Tsuiki E, Kitaoka T, Endo Y, Mishima H, Yoshiura KI, Ogi T, Tanizaki H, Wataya-Kaneda M, Hattori T, Utani A.
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] An immune pathological and ultrastructural skin analysis for rhododenol-induced leukoderma patients2015
Author(s)
Tanemura A, Yang L, Yang F, Nagata Y, Wataya-Kaneda M, Fukai K, Tsuruta D, Ohe R, Yamakawa M, Suzuki T, Katayama I.
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Journal Title
J Dermatol Sci
Volume: 777
Pages: 185-188
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Two Japanease Cases of Birt-Hogg-Dube syndrome with Pulmonary Cysts, Fibrofolliculomas and Renal Cell Carcinoma2014
Author(s)
Yukako MURAKAMI1, MD; Mari WATAYA-KANEDA1, MD, PhD; Mari TANAKA1, MD; Aya TAKAHASHI1, MD; Akira TSUJIMURA2, MD, PhD; Koji INOUE3, MD, PhD; Norio NONOMURA2, MD, PhD; Ichiro KATAYAMA1, MD, PhD
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Journal Title
Case Reports in Dermatolog
Volume: 6
Pages: 20-24
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Guidelines for the diagnosis and treatment of vitiligo in Japan2013
Author(s)
Oiso N, Suzuki T, Wataya-Kaneda M, Tanemura A, Tanioka M, Fujimoto T, Fukai K, Kawakami T, Tsukamoto K, Sano S, Mitsuhashi Y, Nishigori C, Morita A, Nakagawa H, Mizoguchi M, Katayama I, Yamaguchi Y.
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Journal Title
J Dermatol
Volume: 40
Pages: 344-354
DOI
Related Report
Peer Reviewed
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[Presentation] Topical application of Rapamycin Ointment Inhibits Dermato Phagonoidesu Farinae Body (Dfb) Extract Antigen-Induced Dermatitis inNC/Nga Mice2014
Author(s)
Fei Yang, Lingi Yang, Mari Tanaka, Mari Wataya-Tanaka, Ayumi Nakamura, Shoji Matumoto, Mostafa Atitia, Hiroyuki Murota, Ichiro Katayama
Organizer
Annual meetiing of American Academy of Allergy, Asthma and Immunology
Place of Presentation
San Diego, CA, USA
Related Report
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[Presentation] Topical rapamycin therapy is effective against hypomelanotic macules arising in tuberous sclerosis complex A prospective, self-controlled study.2013
Author(s)
M.Tanaka,, M.Wataya-Kaneda, A.Tanemura, Y Kotobuki, S Itoi, A.Nakamura, S.Matsumoto, and I.Katayama
Organizer
2013 International Investigative Dermatology Meeting
Place of Presentation
Edinburgh, Scotland
Related Report
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[Presentation] Topical rapamycin therapy is effective against hypomelanotic macules arising in tuberous sclerosis complex A prospective, self-controlled study.2013
Author(s)
M.Tanaka,, M.Wataya-Kaneda, A.Tanemura, Y Kotobuki, S Itoi, A.Nakamura, S.Matsumoto, and I.Katayama
Organizer
International Pigmented Cell Development Workshop
Place of Presentation
Edinbergh, Scotland
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