Journal of Molecular Neuroscience

, Volume 25, Issue 2, pp 165–169

Humanin attenuates apoptosis induced by DRPLA proteins with expanded polyglutamine stretches

  • Shingo Kariya
  • Makito Hirano
  • Yoshitaka Nagai
  • Yoshiko Furiya
  • Nobuhiro Fujikake
  • Tatsushi Toda
  • Satoshi Ueno
Original Article

DOI: 10.1385/JMN:25:2:165

Cite this article as:
Kariya, S., Hirano, M., Nagai, Y. et al. J Mol Neurosci (2005) 25: 165. doi:10.1385/JMN:25:2:165

Abstract

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal-dominant neurodegenerative disorder caused by expansion of CAG repeats in the DRPLA gene, which codes for a polyglutamine (polyQ) stretch. The expanded polyQs are known to form intracellular aggregates and to confer neurotoxic activity. Recent studies have indicated that activation of apoptosis signal-regulating kinase 1 (ASK1) is involved in polyQ-induced apoptosis. Humanin (HN) is an endogenous peptide that inhibits neuronal cell death caused by mutant Alzheimer’s disease genes, and this neuroprotective factor has recently been reported to suppress apoptosis by inhibiting activation of ASK1. To test the anti-ASK1 effect of HN on polyQ neurotoxicity, we constructed neuronal PC12 cells expressing expanded polyQs under the control of the Tet-Off™ system. Using this cell line, we showed that HN suppresses apoptotic cell death induced by expanded polyQs. However, the suppression was incomplete, suggesting that polyQs also stimulate other pathogenic cascades unrelated to ASK1. We further showed that HN suppresses polyQ aggregate formation. This result implied the possibility that aggregation is also related to the polyQ-mediated cascade involving ASK1 activation. Although the details remain uncertain, our results suggest that ASK1 is potentially involved in pathogenesis of DRPLA and that HN might contribute partially to the suppression of neurodegeneration in polyQ diseases.

Index Entries

Humanin DRPLA polyglutamine ASK1 aggregation apoptosis 

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Shingo Kariya
    • 1
  • Makito Hirano
    • 1
  • Yoshitaka Nagai
    • 2
  • Yoshiko Furiya
    • 1
  • Nobuhiro Fujikake
    • 2
  • Tatsushi Toda
    • 2
  • Satoshi Ueno
    • 1
  1. 1.Department of NeurologyNara Medical UniversityNaraJapan
  2. 2.Division of Functional Genomics, Department of Post-Genomics and DiseasesOsaka University Graduate School of MedicineOsakaJapan

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