Cinnamic acid activates PPAR α to stimulate Lysosomal biogenesis and lower Amyloid plaque pathology in an Alzheimer's disease mouse model.

In this study, we demonstrate that cinnamic acid, a naturally occurring plant-based product, induces lysosomal biogenesis in mouse primary brain cells via upregulation of TFEB. We delineate that cinnamic acid activates the nuclear hormone receptor PPARα to transcriptionally upregulate TFEB and stimulate lysosomal biogenesis. Moreover, using in-silico and biochemical approaches we established that cinnamic acid serves as a potent ligand for peroxisome proliferator-activated receptor α (PPARα). Finally, cinnamic acid treatment in male and female 5× Familial Alzheimer's disease (5XFAD) mice remarkably reduced cerebral amyloid-beta plaque burden and improved memory via PPARα. Therefore, stimulation of lysosomal biogenesis by cinnamic acid may have therapeutic implications for treatment of Alzheimer's disease and other lysosomal disorders originating from accumulation of toxic protein aggregates. PMID: 30578827 [PubMed - as supplied by publisher]
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research