Paper

Hsp104: A Weapon to Combat Diverse Neurodegenerative Disorders
James Shorter

Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA

Address of Corresponding Author

Neurosignals 2008;16:63-74 (DOI: 10.1159/000109760)

  Key Words

• Hsp104
• Prion
• Amyloid
• AAA+ protein
• Huntington's disease
• Neurodegeneration

  Abstract

Many of the fatal neurodegenerative disorders that plague humankind, including Alzheimer's and Parkinson's disease, are connected with the misfolding of specific proteins into a surprisingly generic fibrous conformation termed amyloid. Prior to amyloid fiber assembly, many proteins populate a common oligomeric conformation, which may be severely cytotoxic. Therapeutic innovations are desperately sought to safely reverse this aberrant protein aggregation and return proteins to normal function. Whether mammalian cells possess any such endogenous activity remains unclear. By contrast, fungi, plants and bacteria all express Hsp104, a protein-remodeling factor, which synergizes with the Hsp70 chaperone system to resolve aggregated proteins and restore their functionality. Surprisingly, amyloids can also be adaptive. In yeast, Hsp104 directly regulates the amyloidogenesis of several prion proteins, which can confer selective advantages. Here, I review the modus operandi of Hsp104 and showcase efforts to unleash Hsp104 on the protein-misfolding events connected to disparate neurodegenerative amyloidoses.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

James Shorter, PhD, Department of Biochemistry and Biophysics
University of Pennsylvania School of Medicine
805b Stellar Chance Laboratories, 422 Curie Boulevard
Philadelphia, PA 19104-6059 (USA)
Tel. +1 215 573 4256, Fax +1 215 898 4217, E-Mail jshorter@mail.med.upenn.edu

  Article Information

Published online: December 5, 2007
Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 0, Number of References : 133