Small heat shock proteins: Implications for neurodegeneration & longevity

Aging in general, as well as several age-related diseases, are characterized by a gradual decrease in proper cell functioning. Cells continuously have to deal with protein renewal, degradation and folding. The main hazard of these processes is the formation of partly- or incorrectly folded proteins which tend to form toxic aggregates and disturb cellular functions.
Fortunately, cells contain a special group of proteins devoted to support the process of protein folding. These chaperones can be divided into several families, each with their own characteristic function within the folding network. Within the described research, we focused on the small heat shock protein (sHSP) family. Using both cellular studies and studies in fruit flies, we determined the individual contribution of each sHSP member to protein folding and reduction of aggregation of proteins known to cause neurological disorders such as Huntington’s disease.
Interestingly, we found sHSP members which were only able to support protein folding, while other members were either only effective in reducing protein aggregation or could partially facilitate both processes. Using genetic modulation of these sHSP members in fruit flies, we could subsequently show that only the specific anti-aggregation sHSPs, effective against aggregation of proteins linked to neurological disorders, could reduce degeneration. Furthermore, sHSPs active as protein folders or reducers of aggregation were both able to significantly extend the lifespan of fruit flies, providing additional support for the protein-homeostasis model which describes the important contribution of protein unfolding and aggregation in the aging process.

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	General discussion and perspectives
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