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Hsp60 Friend and Foe of the Nervous System

  • Antonella Marino Gammazza
  • Celeste Caruso Bavisotto
  • Francesca Rappa
  • Federica Scalia
  • Everly Conway de Macario
  • Alberto J. L. Macario
  • Francesco Cappello
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 20)

Abstract

Hsp60 belongs to the subgroup of molecular chaperones named chaperonins and, typically, resides and functions in the mitochondria but it is also present in extramitochondrial sites. It chaperones client peptides as they fold to achieve the native conformation and also displays anti-stress roles by helping stress-damaged proteins regain a functional shape. Thus, Hsp60 is central to the integrity and functionality of mitochondria and energy production. All cells in the nervous system depend on Hsp60 so when the chaperonin malfunctions the consequences on nervous tissues are usually devastating, causing diverse diseases. These are the Hsp60 chaperonopathies, which can be genetic or acquired with the former caused by gene variants and the latter by various post-transcriptional mechanisms. All forms of chaperonopathies, i.e., by defect, by excess, and by mistake, associated with Hsp60 have been described, and some illustrative examples are discussed here. It is clear that this chaperonin is key to neuromuscular physiology but, when qualitatively and/or quantitatively abnormal causes diseases, often very serious.

Keywords

Acquired chaperonopathies Alzheimer’s disease Central nervous system Chaperonins Chaperonopathies Genetic chaperonopathies Hsp60 Leucodystrophies Molecular chaperones Multiple sclerosis Myasthenia gravis Neuropathies Peripheral nervous system Spastic paraplegia 

Abbreviations

Amyloid-β

AChR

Acetylcholine receptor

AD

Alzheimer’s disease

APP

Amyloid precursor protein

BBB

Blood-brain barrier

CCT

Chaperonin containing TCP-1

CNS

Central nervous system

CNV

Copy number variant

CP

Chaperoning system

CSF

Cerebrospinal fluid

CypD

Cyclophilin D

GMB

Glioblastoma multiforme

HIP1

Huntingtin-interacting protein 1

Hsp

Heat shock protein;

HSP

Hereditary spastic paraplegia

IS

Immune system

L-DOPA

3,4-dihydroxy- L-phenylalanine

MECP2

Methyl CpG binding protein 2

MG

Myasthenia gravis

MS

Multiple sclerosis

mtUPR

The mitochondrial unfolded protein response

PBMNc

Peripheral blood mononuclear cells

ROS

Reactive oxygen species

SNP

Single-nucleotide polymorphism

SPG

Spastic paraplegia

TLE

Temporal lobe epilepsy

TRiC

TCP-1 ring complex

WHO

World Health Organization

Notes

Acknowledgements

A.J.L.M, and E.C. de M. were partially supported by IMET. This work was done under the agreement between IEMEST (Italy) and IMET (USA) (this is IMET contribution number IMET 19-007).

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Authors and Affiliations

  • Antonella Marino Gammazza
    • 1
  • Celeste Caruso Bavisotto
    • 1
    • 2
    • 3
  • Francesca Rappa
    • 1
  • Federica Scalia
    • 1
  • Everly Conway de Macario
    • 2
    • 4
  • Alberto J. L. Macario
    • 2
    • 4
  • Francesco Cappello
    • 1
  1. 1.Department of Biomedicine, Neurosciences, and Advanced DiagnosticsUniversity of PalermoPalermoItaly
  2. 2.Euro-Mediterranean Institute of Science and Technology (IEMEST)PalermoItaly
  3. 3.Institute of Biophysics (IBF-CNR)National Research CouncilPalermoItaly
  4. 4.Department of Microbiology and ImmunologyUniversity of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET)BaltimoreUSA

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