Mitochondrial Regulation of Neurodegenerative Proteotoxic Stress
Abstract
The objective of the proposed research is to identify and characterize the basic molecular and metabolic alternations that occur during aging of post-mitotic cells such as neurons under proteotoxic stress in order to understand the etiology of neurodegenerative protcinopathics. The investigators will determine and characterize the chronological life span of Saccharomyces cerevisiae models of polyQ and alpha-synuclein diseases. They will thoroughly determine the effect of polyQ and alpha-synuclein proteins on chronological lifespan and they will characterize the chronology of protein aggregation, mitochondrial function, stress resistance, intracellular reactive oxygen species levels, oxidative protein damage, and accumulation and mobilization of reserve nutrient stores. They will establish the role of mitochondrial function, reactive oxygen species signaling, and oxidative stress in polyQ and alpha-synuclein induced cytotoxicities in aged cells and determine whether manipulation of these pathways suppresses toxicity. Finally, they will explore the connections between pro-survival nutritional cues and mitochondrial functions and determine how they modulate polyQ and alpha-synuclein induced cellular proteotoxicities in chronologically aged cells. Finally, they will validate some of the results obtained in yeast on mitochondrial and nutritional mechanisms of proteotoxicity suppression using an innovative model consisting of human striatal cells differentiated from neuronal stem cells derived from HD patient fibroblasts-induced pluripotent stem cells.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1610311
Entities
People
- Antoni Barrientos
Organizations
- Army Contracting Command
- United States Army
- University of Miami