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Intranasal Administration of Hsp70: Molecular and Therapeutic Consequences

  • Michael B. Evgen’ev
  • David G. Garbuz
  • Alexei V. Morozov
  • Natalia V. Bobkova
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 14)

Abstract

Hsp70 and other molecular chaperones function as a complex neuroprotective system, which fails in the brains of aged people and Alzheimer’s disease (AD)-type neuropathologies. It was demonstrated that intranasally injected exogenous Hsp70 (eHsp70) effectively bypassed the blood-brain barrier and penetrates brain regions of the model animals. It was shown that chronic administration of eHsp70 decreases beta-amyloid level and the number of Aβ-plaques in two mouse models of AD. In both cases eHsp70 restored learning and memory parameters as well as functional state of neurons. Characteristically, eHsp70 treatment increased synaptophysin level and protects neurons in brain areas most affected in AD patients such as hippocampus and neocortex. It was also demonstrated that eHsp70 can promote longevity and life quality in male mice. The eHsp70 treatment decreased accumulation of aging marker lipofuscin and modulates the activity of UPS by increasing expression of several proteasome subunits including immunoproteasome subunit β5i. Deep sequencing studies exploring brain regions of AD-model – 5XFAD mice treated with eHsp70 revealed candidate genes and signal pathways probably underlying beneficial effects of eHsp70 treatment. Taken together, our findings establish intranasal administration of exogenous human Hsp70 as a practical therapeutic approach for the treatment of various neurodegenerative diseases and aging.

Keywords

Aging Deep sequencing Hsp70 Intranasal administration Mouse model of AD 

Abbreviations

AD

Alzheimer’s disease

APP

Amyloid precursor protein

BAG

Bcl-2-associated athanogene-1

BBB

Blood-brain barrier

BSA

Bovine serum albumin

CHIP

Carboxy-terminus of Hsc70-interacting protein

CNS

Central nervous system

Hsp

Heat shock protein

LPS

Lipopolysaccharide

LTA

Lipoteichoic acid

NMDA

N-methyl-D-aspartate receptor

PTZ

Pentylenetetrazole

ROS

Reactive oxygen species

TLR

Toll-like receptor

TNF

Tumor necrosis factor

UPS

Ubiquitin-proteasome system

Notes

Acknowledgments

The work was supported by Russian Science Foundation Grant №14-50-00060 and Program of fundamental research for state academies for 2013-2020 years (N-01201363817).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Michael B. Evgen’ev
    • 1
    • 2
  • David G. Garbuz
    • 1
  • Alexei V. Morozov
    • 1
  • Natalia V. Bobkova
    • 2
  1. 1.Engelhardt Institute of Molecular BiologyMoscowRussia
  2. 2.Institute of Cell Biophysics, RASMoscowRussia

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