NDLI: Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease

Content Provider	Springer Nature : BioMed Central
Author	Xia, Mei-Ling Xie, Xia-Hong Ding, Jian-Hua Du, Ren-Hong Hu, Gang
Abstract	Background Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson’s disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. Methods Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. Results We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. Conclusions Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.
Related Links	https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-020-01791-8.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	17422094
DOI	10.1186/s12974-020-01791-8
Journal	Journal of Neuroinflammation
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2020-04-06
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Neurobiology Immunology Astragaloside IV Astrocyte Cell senescence Mitophagy Parkinson’s disease
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology Cellular and Molecular Neuroscience Neurology
Journal Impact Factor	9.3/2023
5-Year Journal Impact Factor	9.8/2023

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