Rick Morimoto, PhD
Professor
Department of Molecular Biosciences
Northwestern University
(November 29, 2016)
Proteostasis: Stress Responses and Chaperone Networks in Aging and Disease
As the population ages, the incidence of age-related dementia and conditions such Alzheimer’s disease is increasing. While it is understood that the build-up of damaged proteins in the brain is associated with different forms of dementia, how the damage to these proteins occurs is less clear. Dr. Morimoto and his lab are examining how aging and cell response to different stressors affect proteins. Understanding this process could help in the discovery of new treatments or ways to prevent age-related dementia.
Increased lifespan is accompanied by elevated risks for dementia, neurodegeneration and other age-associated degenerative diseases. A common feature of aging and disease is the accumulation of damaged proteins that accumulate in aggregates and amyloid species that interfere with cellular function. The appearance of this “molecular clutter” is a consequence of inherent protein metastability and failure of the protein quality control machinery during aging and stress. In my talk, I examined how the proteostasis network (PN) of molecular chaperones, transport processes, ubiquitin-dependent proteasomes and autophagic machines is essential for proteome health and to prevent the accumulation of protein aggregates. During aging, the composition of the PN and response to heat shock and other cellular stress conditions are compromised with an abrupt transition occurring at reproductive maturity. This signal from the germline stem cells involves an epigenetic mark leading to an irreversible repression of the heat shock response. Likewise, at the organismal level, cell non-autonomous signaling between neurons and surrounding tissues regulates the response to heat shock, and from tissues expressing mutant proteins that communicate to receiving tissues to activate the protective induction of chaperones. Organismal proteostasis therefore represents balance and coordination among multiple cell stress responses to ensure cellular and tissue health and longevity.