Acta Neuropathologica

, Volume 109, Issue 4, pp 367–372 | Cite as

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

  • Shingo Kariya
  • Makito HiranoEmail author
  • Yoshiko Furiya
  • Kazuma Sugie
  • Satoshi Ueno
Regular Paper


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.


MELAS Humanin Ragged-red fibers ATP Mitochondria 



We thank Drs. I. Nishimoto and T. Niikura (Department of Pharmacology and Neuroscience, Keio University School of Medicine) for technical support. We also thank Drs. T. Nakamuro, M. Takamure, M. Kitaguchi, H. Tanaka, M. Ogawa, and H. Shimizu for help with patient recruitment. This study was supported in part by the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Shingo Kariya
    • 1
  • Makito Hirano
    • 1
    Email author
  • Yoshiko Furiya
    • 1
  • Kazuma Sugie
    • 1
  • Satoshi Ueno
    • 1
  1. 1.Department of NeurologyNara Medical UniversityNaraJapan

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