Targeting of intracellular Ca²⁺ stores as a therapeutic strategy against age-related neurotoxicities.

ABSTRACT: Calcium dysregulation often underlies pathologies associated with aging and age-associated neurodegenerative diseases. Cells express a unique pattern of Ca²⁺ channels and pumps geared to fulfill specific physiological requirements and there is a decline in the fidelity of these processes with age and age-associated diseases. J147 is an Alzheimer's disease (AD) drug candidate that was identified using a phenotypic screening platform based upon age-related brain toxicities that are mediated by changes in calcium metabolism. The molecular target for J147 is the α-F1-ATP synthase (ATP5A). J147 has therapeutic efficacy in multiple mouse models of AD and accelerated aging and extends life span in flies. A bioinformatics analysis of gene expression in rapidly aging SAMP8 mice during th

SUBMITTER: Goldberg J 

PROVIDER: S-EPMC7445274 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature