Abstract
Aberrant protein aggregation is mechanistically linked to late onset human neurodegenerations such as Parkinson’s, Huntington’s and Alzheimer’s diseases. Why these disorders emerge late in life is a principal enigma, however, recent results indicate that the aging process plays an active role in enabling their emergence. Perhaps the best characterized regulator of the aging process in worms, flies and mice is the Insulin/IGF-1 Signaling (IIS) pathway. In worms, IIS reduction results in activation of the FOXO-like transcription factor, DAF-16, resulting in enhanced stress resistance and longevity. The benefits associated with reduced IIS are also dependent upon another transcription factor, heat shock factor 1 (HSF-1). Reduced IIS also protects worms from proteotoxicity by regulating opposing activities: HSF-1 promotes disaggregation, while DAF-16 mediates protective active aggregation. The exploration of these mechanisms argues that the IIS enables the emergence of neurodegeneration late in life by reducing cellular capabilities to counter toxic protein aggregation. Here we review the recent studies and discuss the current themes and therapeutic potential of the IIS as a link between the aging process and late onset neurodegenerations
| Original language | American English |
|---|---|
| Title of host publication | Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection |
| Editors | Alexzander A.A. Asea, Ian R. Brown |
| Place of Publication | Dordrecht |
| Publisher | Springer Netherlands |
| Pages | 337-348 |
| Number of pages | 12 |
| ISBN (Print) | 978-1-4020-8231-3 |
| DOIs | |
| State | Published - 2008 |