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Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):16006-11. doi: 10.1073/pnas.1516131112. Epub 2015 Dec 14.

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.

Author information

1
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia;
2
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow, 142290, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia;
3
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia;
4
Institute of Developmental Biology, Moscow, 124319, Russia;
5
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016.
6
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016 evgeny.nudler@nyumc.org.

Abstract

Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of intranasal administration of exogenous recombinant human Hsp70 (eHsp70) on lifespan and neurological parameters in middle-aged and old mice. Long-term administration of eHsp70 significantly enhanced the lifespan of animals of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70 administration demonstrated improved learning and memory in old mice. Likewise, the investigation of locomotor and exploratory activities after eHsp70 treatment demonstrated a significant therapeutic effect of this chaperone. Measurements of synaptophysin show that eHsp70 treatment in old mice resulted in larger synaptophysin-immunopositive areas and higher neuron density compared with control animals. Furthermore, eHsp70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain and enhanced proteasome activity. The potential of eHsp70 intranasal treatment to protect synaptic machinery in old animals offers a unique pharmacological approach for various neurodegenerative disorders associated with human aging.

KEYWORDS:

Hsp70; aging; memory; proteasome; therapy

PMID:
26668376
PMCID:
PMC4702952
DOI:
10.1073/pnas.1516131112
[Indexed for MEDLINE]
Free PMC Article

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