Enhanced skeletal muscle proteostasis as a determinant of CNS protein quality control and neural function in the aging brain
Description: Project Narrative The importance of proteostasis to health and disease is well documented, yet how this process is regulated in a whole organism context remains poorly understood, especially in mammals. Individual organs in the body, particularly skeletal muscle, may play a pivotal role in regulating proteostasis in other tissues; hence, this project investigates the role of skeletal muscle-expressed Transcription factor E-B (TFEB), a master transcription factor regulator of autophagy and cellular clearance, in promoting CNS proteostasis during aging. These studies will address muscle-to-brain cell-non autonomous proteostasis signaling, determine if enhanced skeletal muscle proteostasis is capable of promoting neuroprotection, uncover the mechanistic basis for this effect, develop powerful new models for testing mitophagy/autophagy activity in the aging CNS, and establish if soluble factors secreted by muscle ("myokines") mediate beneficial CNS effects in conditional skeletal muscle-expressing TFEB transgenic mice, in the hope that such work may yield therapeutic opportunities for promoting CNS quality control pathways and function in age-related brain diseases.
Funder: National Institute on Aging
Funding type: research
Funder scheme: RF1
Start date: 2017-09-15
End date: 2022-08-31
Investigator: CONSTANZA JAVIERA CORTES
Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 7
Funder award ID: RF1AG057264
OpenAlex ID: G1460544590