Journal of Experimental Gerontology . 2023 Jan;17
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Journal of Experimental Gerontology
. 2023 Jan;171:112037. doi: 10.1016/j.exger.2022.112037. Epub 2022 Nov 24.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) prevents the neuroinflammation induced dopaminergic neurodegeneration
Authors
epartment of Neurology, Tongji Hospital, School of Medicine, Tongji University, Shanghai
Results: Our findings indicated that the elevated MANF expression by the AAV8-MANF administration ameliorated the motor dysfunction and protected the dopaminergic neurons in the 6-OHDA treated rats. The upregulated CD11b in the rat SN caused by the 6-OHDA administration was significantly attenuated by the pretreatment of the AAV8-MANF. Furthermore, the levels of p-AKT, p-GSK3β, BCL-2, and Nrf-2 were upregulated by the high expression of the MANF. Under the oxidative stress of the 6-OHDA, the MANF significantly reduced the apoptotic effect of the TNF-α on the SH-SY5Y cells. In the LPS treated BV-2 cells, the MANF reduced the production of the TNF-α and IL-6, via enhancing the Nrf-2, p-Akt, p-GSK3β, and p-NF-κβ level.
Conclusions: These results suggested that the MANF prevented the dopaminergic neurodegeneration caused by the microglia activation in PD via activation of the AKT/GSK3β-Nrf-2 signaling axis.
https://pubmed.ncbi.nlm.nih.gov/36436758/
. 2023 Jan;171:112037. doi: 10.1016/j.exger.2022.112037. Epub 2022 Nov 24.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) prevents the neuroinflammation induced dopaminergic neurodegeneration
Authors
epartment of Neurology, Tongji Hospital, School of Medicine, Tongji University, Shanghai Results: Our findings indicated that the elevated MANF expression by the AAV8-MANF administration ameliorated the motor dysfunction and protected the dopaminergic neurons in the 6-OHDA treated rats. The upregulated CD11b in the rat SN caused by the 6-OHDA administration was significantly attenuated by the pretreatment of the AAV8-MANF. Furthermore, the levels of p-AKT, p-GSK3β, BCL-2, and Nrf-2 were upregulated by the high expression of the MANF. Under the oxidative stress of the 6-OHDA, the MANF significantly reduced the apoptotic effect of the TNF-α on the SH-SY5Y cells. In the LPS treated BV-2 cells, the MANF reduced the production of the TNF-α and IL-6, via enhancing the Nrf-2, p-Akt, p-GSK3β, and p-NF-κβ level.
Conclusions: These results suggested that the MANF prevented the dopaminergic neurodegeneration caused by the microglia activation in PD via activation of the AKT/GSK3β-Nrf-2 signaling axis.
https://pubmed.ncbi.nlm.nih.gov/36436758/
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