Journal
ACS CHEMICAL NEUROSCIENCE
Volume 12, Issue 23, Pages 4428-4437Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00468
Keywords
Alzheimer's disease; autophagy; SIRT5; oxidative stress
Funding
- Hei Longjiang Province Post-doctoral Research Funding Project [LBH-Z20032]
- Scientific Research Project of Heilongjiang Health and Family Planning Commission [2020-241]
Ask authors/readers for more resources
The study revealed that SIRT5 plays a crucial role in the treatment of Alzheimer's disease (AD), as its overexpression can ameliorate AD progression by activating autophagy, reducing oxidative stress, and protecting neurons by inhibiting activated microglia and astrocytes. This therapeutic approach shows promise for AD treatment.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in elderly individuals and characterized by impaired cognition and accumulation of beta-amyloid (A beta). Activating autophagy to clear A beta is a plausible approach for AD treatment. The levels of A beta and autophagy signaling factors in APP695/PS1-dE9 transgenic (APP/PS1) mice were detected by immuno histological analysis, real-time PCR, and the western blotting assay. The progression of AD was determined by A beta levels, activated neurons (MAP2+), and microglia (Iba-1(+)). The learning ability was measured using a Morris water maze. Reactive oxygen species (ROS) production, malondialdehyde (MDA) levels, and mitochondrial superoxide dismutase (SOD) activity were checked to determine oxidative stress. AD mice exhibited impaired autophagy and a decreased level of SIRT5. SIRT5 overexpression promoted autophagy, manifested by elevated Becn1 and ratio of LC3b-II/I, as well as suppressed oxidative stress. The SIRT5-ameliorated neuron damage was correlated with suppressed activation of microglia and astrocytes. Elevated SIRT5 expression decreased the inflammation in AD brains and neurons. Inhibition of autophagy abolished the protective role of SIRT5 in neurons during AD. Our findings suggested that SIRT5 overexpression could ameliorate the progression of AD both in vitro and in vivo through activating autophagy. We presented ectopic expression of SIRT5 as a promising therapeutic approach for AD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available