Alteration of protein folding and degradation in motor neuron diseases: Implications and protective functions of small heat shock proteins

Serena Carra, Valeria Crippa, Paola Rusmini, Alessandra Boncoraglio, Melania Minoia, Elisa Giorgetti, Harm H. Kampinga, Angelo Poletti*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

50 Citations (Scopus)

Abstract

Motor neuron diseases (MNDs) are neurodegenerative disorders that specifically affect the survival and function of upper and/or lower motor neurons. Since motor neurons are responsible for the control of voluntary muscular movement, MNDs are characterized by muscle spasticity, weakness and atrophy. Different susceptibility genes associated with an increased risk to develop MNDs have been reported and several mutated genes have been linked to hereditary forms of MNDs. However, most cases of MNDs occur in sporadic forms and very little is known on their causes. Interestingly, several molecular mechanisms seem to participate in the progression of both the inherited and sporadic forms of MNDs. These include cytoskeleton organization, mitochondrial functions, DNA repair and RNA synthesis/processing, vesicle trafficking, endolysosomal trafficking and fusion, as well as protein folding and protein degradation. In particular, accumulation of aggregate-prone proteins is a hallmark of MNDs, suggesting that the protein quality control system (molecular chaperones and the degradative systems: ubiquitin-proteasome-system and autophagy) are saturated or not sufficient to allow the clearance of these altered proteins. In this review we mainly focus on the MNDs associated with disturbances in protein folding and protein degradation and on the potential implication of a specific class of molecular chaperones, the small heat shock proteins (sHSPs/HSPBs), in motor neuron function and survival. How boosting of specific HSPBs may be a potential useful therapeutic approach in MNDs and how mutations in specific HSPBs can directly cause motor neuron degeneration is discussed. (C) 2011 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)83-100
Number of pages18
JournalProgress in Neurobiology
Volume97
Issue number2
DOIs
Publication statusPublished - May-2012

Keywords

  • Neurodegeneration
  • Motor neuron diseases
  • Spinal and bulbar muscular atrophy
  • Amyotrophic lateral sclerosis
  • Small heat shock proteins
  • Autophagy
  • HSPB8
  • Protein misfolding
  • Protein aggregation
  • SBMA
  • ALS
  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • BULBAR MUSCULAR-ATROPHY
  • MARIE-TOOTH-DISEASE
  • AGGREGATE-PRONE PROTEINS
  • UBIQUITIN-PROTEASOME SYSTEM
  • ANDROGEN RECEPTOR PROTEIN
  • TRANSGENIC MOUSE MODEL
  • RAT SPINAL-CORD
  • EXPANSION NEURODEGENERATIVE DISEASE
  • ELONGATED POLYGLUTAMINE TRACT

Cite this