ReferenceID 126
Cinnamic acid activates PPARα to stimulate Lysosomal biogenesis and lower Amyloid plaque pathology in an Alzheimer's disease mouse model
Neurobiol Dis
The response of the lysosomes, the waste clearance machinery of the cell, to different environmental stimuli is coordinated by a gene network with a master regulator Transcription factor EB (TFEB) at the core. Disruption
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Record Fields
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- Reference Id
- 126
- Evidence Id
- 16716
- Core Evidence Id
- 16716
- Source Reference Id
- 213
- Herb2 Reference Id
- HBREF000412
- Subject Paper Key
- HBIN020657_30578827
- Pubmed Id
- 30578827
- Doi
- 10.1016/j.nbd.2018.12.007
- Paper Title
- Cinnamic acid activates PPARα to stimulate Lysosomal biogenesis and lower Amyloid plaque pathology in an Alzheimer's disease mouse model
- Paper Abstract
- The response of the lysosomes, the waste clearance machinery of the cell, to different environmental stimuli is coordinated by a gene network with a master regulator Transcription factor EB (TFEB) at the core. Disruption of multiple facets of the lysosomal and autophagic network has been linked to various neurodegenerative and lysosomal storage disorders, making TFEB an attractive therapeutic target to rescue or augment lysosomal function under pathological scenario. 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.
- Journal
- Neurobiol Dis
- Publish Year
- 2019
- Experiment Subject
- mouse primary brain cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Alzheimer's Disease
- Paper Title Cn
- Paper Title En
- Cinnamic acid activates PPARα to stimulate Lysosomal biogenesis and lower Amyloid plaque pathology in an Alzheimer's disease mouse model
- Bilingual Status
- semi_complete