DOI: 10.1002/ame2.12341
The sigma-1 receptor-TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis
Jianlun Ji1
Ce Gao1
Qinghua Wang2
Xiaoxia Jia2
Hao Tian3
Yaqin Wei2
Zhidong Liu1
Yun Wang2
Lin Guo1
1.Department of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,China;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,China2.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,China3.Agro-Products Processing Research Institute,Yunnan Academy of Agricultural Sciences,Kunming,China
摘要：Background:Therapy in the latent period is favorable for retarding the process of epileptogenesis.Recently,we have discovered that the activated sigma-1 receptor(Sig-1R)attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis.But the molecular mechanism needs further investigation.
Methods:PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice.After the treatment of PRE-084,the pro-inflammatory cytokines,neuropathological traits,and the level of mitochondrial translocator assembly and maintenance 41 homolog(TAMM41)in the hippocampus were examined.The mode in which the Sig-1R interacts with TAMM41 was explored.The role of TAMM41 in the protecting effect of PRE-084 was established.
Results:PRE-084 inhibited the growth of pro-inflammatory cytokines,reduced the formation of gliosis,alleviated neuronal damage in the hippocampus,and attenu-ated memory impairment in the latent period of epileptogenesis.The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice.The Sig-1R bound with TAMM41 directly,maintaining the stability of TAMM41.Knockdown of TAMM41 reversed the protective effect of PRE-084,and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084.
Conclusion:We presented the concept of the"sigma-1 receptor-TAMM41 axis"and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.
机标关键词：memorylatentperiodaxisattenuatesduringepileptogenesiseuro
论文发表日期：2025-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 197-208 )
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