Abstract：
:A significant pathological feature of refractory temporal lobe epilepsy (TLE) is neuronal loss. Oxidative stress caused by repeated seizures is an important mechanism leading to neuronal loss in hippocampus. Nicotinamide-adenine dinucleotide (NAD) a coenzyme that is involved in many biochemical oxidation-reduction reactions. Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) catalyzes an essential step in NAD (NADP) biosynthetic pathwayhas and been considered as a neuronal maintenance factor that protect neurons against insults through context-dependent mechanism. However, it is unexpected that Nmnat2 does not play a neuroprotective role in epilepsy. We found that Nmnat2 was increased in mice model of TLE. Gain-of-function approach revealed that overexpression of Nmnat2 in CA1 area enhanced seizure susceptibility and caused neuronal loss in vivo. Moreover, we found that the chaperone function was essential to increased apoptosis through the function mutation of Nmnat2. Finally, Nmnat2 overexpression in vivo reduced in expression of SOD2 and increased FoxO3a. Overall, our study discloses a new biological function of Nmnat2 in epilepsy and provides novel insights into the molecular events underlying epilepsy.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
Wu H,Meng Q,Zhang Y,Li H,Liu Y,Dong S,Liu B,Zhang Hdoi
10.1016/j.brainresbull.2020.11.019subject
Has Abstractpub_date
2021-02-01 00:00:00pages
1-10eissn
0361-9230issn
1873-2747pii
S0361-9230(20)30705-Xjournal_volume
167pub_type
杂志文章abstract：:Brief cerebral ischemia leads to selective neuronal necrosis (SNN), which is characterized by neuronal death with sparing of glial and vascular elements of the central nervous system. Understanding the pathophysiology of SNN may help elucidating the mechanisms and consequences of neuronal injury in humans following br...
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journal_title：Brain research bulletin
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pub_type： 杂志文章
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journal_title：Brain research bulletin
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pub_type： 杂志文章
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journal_title：Brain research bulletin
pub_type： 杂志文章
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journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2006.06.006
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pub_type： 杂志文章,评审
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journal_title：Brain research bulletin
pub_type： 杂志文章
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journal_title：Brain research bulletin
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
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journal_title：Brain research bulletin
pub_type： 杂志文章
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journal_title：Brain research bulletin
pub_type： 杂志文章
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更新日期：2020-05-01 00:00:00
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pub_type： 杂志文章
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