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.