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Acta Neuropathologica
Published in: Acta Neuropathologica 4/2005

01-04-2005 | Regular Paper

Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent

Authors: Shingo Kariya, Makito Hirano, Yoshiko Furiya, Kazuma Sugie, Satoshi Ueno

Published in: Acta Neuropathologica | Issue 4/2005

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Abstract

Humanin (HN) was originally identified as an endogenous peptide that protects neuronal cells from apoptosis induced by various types of Alzheimer’s disease-related insults. We have previously indicated that HN increases cellular ATP levels and speculated that this peptide may rescue energy-deficient cells in mitochondrial disorders. Here, we report, for the first time, increased HN expression in skeletal muscles from patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). HN was strongly positive in all ragged-red fibers (RRFs) and some non-RRFs, and most of them were type 1 fibers generally requiring higher energy than type 2 fibers. HN in these fibers was localized in mitochondria. HN expression was also increased in small arteries that strongly reacted for succinate dehydrogenase. Our experiments on muscular TE671 cells indicated the possibility that synthesized HN increases cellular ATP levels by directly acting on mitochondria. From these in vivo and in vitro findings, we propose that HN expression might be induced in response to the energy crisis within affected fibers and vessels in MELAS muscles and further be a possible therapeutic candidate for MELAS.
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Metadata
Title
Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent
Authors
Shingo Kariya
Makito Hirano
Yoshiko Furiya
Kazuma Sugie
Satoshi Ueno
Publication date
01-04-2005
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 4/2005
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-004-0965-5

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