Journal of Molecular Neuroscience

, Volume 30, Issue 3, pp 249–265

Chaperones and proteases

Cellular fold-controlling factors of proteins in neurodegenerative diseases and aging
  • Marie-Pierre Hinault
  • Anat Ben-Zvi
  • Pierre Goloubinoff
Review

DOI: 10.1385/JMN:30:3:249

Cite this article as:
Hinault, M., Ben-Zvi, A. & Goloubinoff, P. J Mol Neurosci (2006) 30: 249. doi:10.1385/JMN:30:3:249

Abstract

The formation of toxic protein aggregates is a common denominator to many neurode generative diseases and aging. Accumulation of toxic, possibly infectious protein aggregates induces a cascade of events, such as excessive inflammation, the production of reactive oxygen species, apoptosis and neuronal loss. A network of highly conserved molecular chaperones and of chaperone-related proteases controls the fold-quality of proteins in the cell. Most molecular chaperones can passively prevent protein aggregation by binding misfolding inter mediates. Some molecular chaperones and chaperone-related proteases, such as the proteasome, can also hydrolyse ATP to forcefully convert stable barmful protein aggregates into harmless natively refoldable, or protease-degradable, polypeptides. Molecular chaperones and chaperone-related proteases thus control the delicate balance between natively folded functional proteins and aggregation-prone misfolded proteins, which may form during the lifetime and lead to cell death. Abundant data now point at the molecular chaperones and the proteases as major clearance mechanisms to remove toxic protein aggregates from cells, delaying the onset and the outcome of protein-misfolding diseases. Therapeutic approaches include treatments and drugs that can specifically induced and sustain a strong chaperone and protease activity in cells and tissues prone to toxic protein aggregations.

Index Entries

Proteasomeheat shock proteinsHsp70Hsp90Hsp27NSAIDsinflammationaggresomefever

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Marie-Pierre Hinault
    • 1
  • Anat Ben-Zvi
    • 2
  • Pierre Goloubinoff
    • 1
  1. 1.DBMV, Faculty of Biology and MedicineLausanne UniversityLausanneSwitzerland
  2. 2.Rice Institute for Biomedical Research, Department of Biochemistry, Molecular Biology, and Cell BiologyNorthwestern UniversityEvanston