Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease
| Autor: | Xia-Hong Xie, Mei-Ling Xia, Ren-Hong Du, Gang Hu, Jian-Hua Ding |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Senescence
Male Immunology Astragaloside IV Neuroprotection lcsh:RC346-429 Cellular and Molecular Neuroscience Mice Parkinsonian Disorders Mitophagy medicine Aging brain Animals Cellular Senescence lcsh:Neurology. Diseases of the nervous system Pars compacta Chemistry General Neuroscience Research Dopaminergic Neurons Neurodegeneration Autophagy Saponins medicine.disease Triterpenes Cell biology medicine.anatomical_structure Neuroprotective Agents Neurology Astrocytes Nerve Degeneration Parkinson’s disease Cell senescence Astrocyte |
| Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-13 (2020) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/s12974-020-01791-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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