MSc Exit Seminar- Paige O’Leary (Brown Lab)

Induction of Heat Shock Proteins in Differentiated Human SH-SY5Y Neuronal Cells by Caffeine and Cafestol

During aging, protein quality control fails, leading to the accumulation of misfolded, aggregation-prone proteins which are characteristic of neurodegenerative diseases for which few effective therapies exist. Enhancement of protein quality control mechanisms is a potential treatment strategy, specifically upregulation of heat shock proteins (Hsps) that function to counteract misfolded proteins. Non-toxic inducers are required that can be ingested regularly and cross the blood-brain barrier to trigger Hsp induction in neurons that are affected in neurodegenerative diseases. Caffeine is a non-toxic compound taken daily that crosses the blood-brain barrier. The effects of two coffee components namely, caffeine and cafestol, are examined on the induction and intracellular localization of Hsps in differentiated human neuronal cells grown in tissue culture. Cafestol, but not caffeine, induced HSPA1A (Hsp70-1) and the little studied HSPA6 (Hsp70B’) which localized to the nucleolus where these Hsps could protect ribosome biogenesis, a critical feature of neuronal protein synthesis.