Therapeutic effect of exogenous Hsp70 in mouse models of Alzheimer's disease

Natalia V. Bobkova, David G. Garbuz, Inna Nesterova, Natalia Medvinskaya, Alexander Samokhin, Irina Alexandrova, Valerii Yashin, Vadim Karpov, Michail S. Kukharsky, Natalia N. Ninkina, Andrey A. Smirnov, Evgeny Nudler, Michael Evgen'Ev

Research output: Contribution to journalArticlepeer-review

Abstract

Brain deterioration resulting from 'protein folding' diseases, such as the Alzheimer's disease (AD), is one of the leading causes of morbidity and mortality in the aging human population. Heat shock proteins (Hsps) constitute the major cellular quality control system for proteins that mitigates the pathological burden of neurotoxic protein fibrils and aggregates. However, the therapeutic effect of Hsps has not been tested in a relevant setting. Here we report the dramatic neuroprotective effect of recombinant human Hsp70 in the bilateral olfactory bulbectomy model (OBX mice) and 5XFAD mouse models of neurodegeneration. We show that intranasally-administered Hsp70 rapidly enters the afflicted brain regions and mitigates multiple AD-like morphological and cognitive abnormalities observed in model animals. In particular, in both cases it normalizes the density of neurons in the hippocampus and cortex which correlates with the diminished accumulation of amyloid-β (Aβ) peptide and, in the case of 5XFAD mice, reduces Aβ plaque formation. Consistently, Hsp70 treatment also protects spatial memory in OBX and 5XFAD mice. These studies demonstrate that exogenous Hsp70 may be a practical therapeutic agent for treatment of neurodegenerative diseases associated with abnormal protein biogenesis and cognitive disturbances, such as AD, for which neuroprotective therapy is urgently needed.

Original languageEnglish
Pages (from-to)425-435
Number of pages11
JournalJournal of Alzheimer's Disease
Volume38
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • 5XFAD mice
  • Alzheimer's disease
  • Hsp70
  • amyloid-β
  • bulbectomized mice

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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