Journal
ONCOTARGET
Volume 7, Issue 46, Pages 74484-74495Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12811
Keywords
ampelopsin; aging; autophagy; miR-34a; SIRT1-mTOR signal pathway; Gerotarget
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Funding
- National Natural Science Foundation of China [31571228, 81601228]
- Chutian Scholar Program
- Hubei Superior Discipline Groups of Physical Education and Health Promotion from the Education Department of Hubei Province
- Innovative Start-up Foundation from Wuhan Sports University
- Youth Faculty Foundation from Wuhan Sports University [2016QZ04]
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The underlying molecular mechanisms for aging-related neurodegenerative diseases such as Alzheimer's disease (AD) are not fully understood. Currently, growing evidences have revealed that microRNAs (miRNAs) are involved in aging and aging-related diseases. The up-regulation of miR-34a has been reported to be associated with aging-related diseases, and thus it should be a promising therapeutic target. Ampelopsin, also called dihydromyricetin (DHM), a natural flavonoid from Chinese herb Ampelopsis grossedentata, has been reported to possess multiple pharmacological functions including anti-inflammatory, anti-oxidative and anticancer functions. Meanwhile, it has also gained tremendous attention against neurodegenerative diseases as an anti-aging compound. In the present study, the model rats with D-gal-induced brain aging revealed an obvious expression of miR-34a; in contrast, it could be significantly suppressed upon DHM treatment. In addition, target genes associated with miR-34a in the presence of DHM treatment were also explored. DHM supplementation inhibited D-gal-induced apoptosis and rescued impaired autophagy of neurons in hippocampus tissue. Moreover, DHM activated autophagy through up-regulated SIRT1 and down-regulated mTOR signal pathways due to the down-regulated miR-34a. In conclusion, DHM can execute the prevention and treatment of D-gal-induced brain aging by miR-34a-mediated SIRT1-mTOR signal pathway.
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