Bushen Huoxue acupuncture ameliorates Alzheimer's disease by upregulating MARCHF3 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis.

Autor: Zhu H; Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410008, Hunan Province, China., Zhang T; Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410008, Hunan Province, China., Li R; Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410008, Hunan Province, China., Ren D; Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410008, Hunan Province, China., Xu J; Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410008, Hunan Province, China., Xiao L; Department of Traditional Chinese Medicine, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410008, Hunan Province, China. xy3yy_xiaolan@126.com.
Jazyk: angličtina
Zdroj: Metabolic brain disease [Metab Brain Dis] 2024 Nov 18; Vol. 40 (1), pp. 11. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1007/s11011-024-01459-9
Abstrakt: Alzheimer's disease (AD) is a common neurodegenerative disorder that places a heavy burden on patients and society. Hippocampal neuronal loss is a hallmark of AD progression. Therefore, understanding the mechanism underlying hippocampal neuronal death would be of great importance for the diagnosis and treatment of AD. This study aimed to explore the molecular mechanism via which Bushen Huoxue Acupuncture inhibits hippocampal neuronal pyroptosis in AD. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as a model of AD. Bushen Huoxue Acupuncture was performed in four acupoints: "Baihui acupoint" (GV20), "Shenshu acupoint" (BL23), "Xuehai acupoint" (SP10), and "Geshu acupoint" (BL17). Morris water maze was used to test cognitive function in mice. IHC staining was used to test mice's Aβ1-42, MARCHF1 and MARCHF3 expression. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining was used for observing hippocampal neuronal apoptosis. The mRNA expression levels of pyroptosis markers MARCHF1, MARCHF3, NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 mRNA in AD mice were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The protein expression of NLRP3, caspase-1 and GSDMD-N was tested by Western blotting. IL-1β and IL-18 protein levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). SH-SY5Y cells were used to establish an AD model following Aβ 1-42 treatment. Western blot was used to detect the NLRP3, MARCHF1 and MARCHF3 proteins following Aβ 1-42 treatment. The endogenous Co-IP assay in combination with immunoblotting for ubiquitin signals was used to detect of NLRP3 ubiquitination level. We found that Bushen Huoxue Acupuncture protected cognitive impairment in AD mice. Bushen Huoxue Acupuncture inhibited hippocampal neuronal pyroptosis and the secretion of inflammatory cytokines in vivo. In SH-SY5Y cells, we found that Aβ 1-42 decreased the binding of E3 ubiquitin-protein ligase MARCHF1 or MARCHF3 with NLRP3, and the ubiquitination of NLRP3. In conclusion, Bushen Huoxue Acupuncture ameliorates AD by upregulating MARCHF3 to induce NLRP3 ubiquitination and inhibits caspase-1-dependent pyroptosis.
Competing Interests: Declarations Consent for publication The data used in this study has never been published before. Competing interests The authors declare no competing interests. Conflict of interest The authors declare that they have no competing interests. Ethics approval All animal experiments were conducted with the approval of the Experimental Animal Ethics Committee of The Third Xiangya Hospital of Central South University. All protocols were performed under conditions to minimize animal suffering. Consent to participate Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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