Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Bobkova, N. V., Garbuz, D. G., Nesterova, I., Medvinskaya, N., Samokhin, A., Alexandrova, I., Yashin, V., Karpov, V., Kukharsky, M. S., Ninkina, Natalia, Smirnov, A. A., Nudler, E. and Evgen'ev, M. 2014. Therapeutic effect of exogenous Hsp70 in mouse models of Alzheimer's disease. Journal of Alzheimer's Disease 38 (2) , pp. 425-435. 10.3233/JAD-130779

[img]
Preview
PDF - Published Version
Download (704kB) | Preview

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: IOS Press
ISSN: 1387-2877
Date of First Compliant Deposit: 20 February 2019
Last Modified: 20 Feb 2019 16:55
URI: http://orca.cf.ac.uk/id/eprint/68641

Citation Data

Cited 59 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics