ABSTRACT
Many human degenerative diseases are characterized by the progressive degeneration
of neurons and accompanying production of abnormal intracellular inclusions. These
inclusions are composed of once normal cellular proteins [e.g., neurofibrillary tangles in
Alzheimer’s disease (AD)] and are also generally found to contain the small heat shock
protein (hsp’s) ubiquitin and hsp70. These observations suggest that hsp’s are associated
with the etiology of these diseases, or that their up-regulation represents an unsuccessful
attempt to remove the abnormal protein aggregates. A number of recent studies (and novel
data presented in this review) have shown that the overexpression of hsp70 and/or hsp40
is neuroprotective for the polyglutamine disorders. Furthermore, genetic studies clearly
show that abnormalities in the ubiquitin proteosome system (UPS) underlie some forms of
Parkinson’s disease (PD). These observations suggest that manipulating hsp expression
to facilitate both the refolding and removal of abnormal proteins could be therapeutic for
many human neurodegenerative conditions.