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Hsp70-Family Proteins and Neurodegenerative Diseases

  • Zheying Sun
  • Roy J. Blackburn
  • Laura J. Blair
  • John KorenIII
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 14)

Abstract

Neuronal proteostasis is a highly regulated and crucial component of neural function. Unlike other tissues and organ, cell loss due to damage and dysfunctional signaling mechanisms is not an option for the brain. Neurons are thusly dependent on the collective cellular machinery of the molecular chaperones. Hsp70, a molecular chaperone which hydrolyzes ATP to fold proteins into a functional state, has been implicated as both a driver of disease pathogenesis and a therapeutic target for the activities and associations identified in several neurodegenerative diseases. Through interaction studies, genetic models, and small molecule therapeutics which serve as chemical tools, we have gained a greater understanding and appreciation for the role of Hsp70 in several neurodegenerative diseases. This chapter will discuss the studies and tools which elucidated the role of Hsp70 family members in neurodegenerative disorders and will offer perspective into therapeutic interventions which may prove beneficial for treating these diseases.

Keywords

Alzheimer’s disease Hsp70 Molecular chaperones Neurodegenerative diseases Parkinson’s disease 

Abbreviations

α-syn

α-synuclein

Amyloid beta

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

BAG-1

Bcl2-associated athanogene-1

CHIP

c-terminus of Hsc70 interacting protein

CME

Clatherin-mediated endocytosis

fALS

Familial Amyotrophic lateral sclerosis

GA

Geldanamycin

HD

Huntington’s disease

Hsc

Heat shock cognate

Hsp

Heat shock protein

LRRK2

Leucine-rich repeat kinase 2

MAPT, tau

Microtubule associating protein tau

PCR

Polymerase chain reaction

PD

Parkinson’s disease

polyQ

Polyglutamine-expansions

SCA

Spinocerebellar ataxia

SNpc

Substantia nigra pars compacta

SOD1

Superoxide dismutase 1

TDP-43

TAR DNA binding protein 43

UPS

Ubiquitin-proteasome system

Notes

Acknowledgements

This book chapter is dedicated to the life and memory of Dr. Chad A. Dickey. We apologize to the many authors who have contributed to our understanding of the molecular chaperone and neurodegenerative disease fields, and whose work we have failed to discuss or cite.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Zheying Sun
    • 1
  • Roy J. Blackburn
    • 1
  • Laura J. Blair
    • 1
  • John KorenIII
    • 1
  1. 1.Department of Molecular Medicine, College of MedicineUSF Byrd Alzheimer’s Institute, University of South FloridaTampaUSA

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