Abstract
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 anti-cancer 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.
Highlights
Alzheimer’s disease (AD) is the most prevalent aging-associated neurodegenerative disease in the population with over 65 years old
Increasing evidence suggests that the alteration in miRNA expression could be implicated in the pathogenesis of AD. miR-34a is a critical player for the induction of senescence, cell cycle arrest and apoptosis, which is highly correlated with a variety www.impactjournals.com/oncotarget of aging-related diseases including AD [5]
The spatial learning and memory capacity of D-galinduced aging rats was evaluated by morris water maze (MWM) test
Summary
Alzheimer’s disease (AD) is the most prevalent aging-associated neurodegenerative disease in the population with over 65 years old. The regulation of non-coding RNAs has gained tremendous interest and attention [2]. MicroRNAs (miRNAs) are small non-coding RNAs with 18-25 nucleotides in length, and can negatively regulate mRNA stability and protein expression. MiRNAs are abundant in brain and play an important role in neurodevelopment, synaptic plasticity and pathogenesis of neurodegenerative disorders [3, 4]. MiR-34a is a critical player for the induction of senescence, cell cycle arrest and apoptosis, which is highly correlated with a variety www.impactjournals.com/oncotarget of aging-related diseases including AD [5]. This finding highlights the fact that miRNAs could be the novel targets for pharmacological interventions
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
