2012 Fiscal Year Final Research Report
Search for neuronal cell death-inhibiting drugs for Alzheimer's disease-relevant signal transduction
Project/Area Number |
22590247
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | Tokyo Medical University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
MATSUOKA Masaaki 東京医科大学, 医学部, 教授 (70222297)
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Project Period (FY) |
2010 – 2012
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Keywords | アルツハイマー病 / 神経細胞死 / アミロイド前駆体蛋白質 / プレセニリン / ヒューマニン |
Research Abstract |
In this research program, we have examined the neuronal cell death mechanism underlysing Alzhemer’s disease (AD), and identified an antagonist of Humanin (HN) which inhibited AD-relevant neuronal cell death and an endogenous agonist of HN receoptor complex composed of WSX-1, ciliary neurotrophic factor receptor/gp130. The results were: (1) MOCA is the key molecule that unifies APP-mediated death signal to PS-mediated death signal, (2) V-set transmembrane domain containing 2 like inhibited HN’s activity via direct binding, and (3) A series of experiments also showed that calmodulin-like skin protein (CLSP), highly expressed in skin tissues, is transported across blood-brain barrier to the central nervous system. CLSP inhibited familial AD-linked V642I-APP-induced neuronal cell death via its binding to HN receptor following activation of JAK2/STAT3 axisThese results suggest that CLSP play a main role in inhibiting AD-related neuronal death and dysfunction in vivo as a physiological defense factor.
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[Journal Article] Caricasole AVSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin2011
Author(s)
Rossini L, Hashimoto Y, Suzuki H, Kurita M, Gianfriddo M, Scali C, Roncarati R, Franceschini D, Pollio G, Trabalzini L, Terstappen GC, Matsuoka M
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Journal Title
FASEB J.
Volume: 25
Pages: 1983-2000
DOI
Peer Reviewed
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