Impaired TNF-alpha control of IP3R-mediated Ca2+ release in Alzheimer's disease mouse neurons.
Impaired TNF-alpha control of IP3R-mediated Ca2+ release in Alzheimer's disease mouse neurons.
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DOI：
10.1016/j.cellsig.2009.11.006
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发表时间：
2010-03
影响因子：
4.8
通讯作者：
Bowers WJ
中科院分区：
文献类型：
--
作者：
Park KM;Yule DI;Bowers WJ
The misguided control of inflammatory signaling has been previously implicated in the pathogenesis of several neurological disorders, including Alzheimer's disease (AD). Induction of tumor necrosis factor-alpha (TNF-α), a central mediator of neuroinflammation, occurs commensurate with the onset of early disease in 3xTg-AD mice, which develop both amyloid plaque and neurofibrillary tangle pathologies in an age- and region-dependent pattern. Herein, we describe regulation inherent to 3xTg-AD neurons, which results in the loss of TNF-α mediated enhancement of inositol 1,4,5 trisphosphate (IP3R)-mediated Ca2+ release. This modulation also leads to significant down regulation of IP3R signaling following protracted cytokine exposure. Through the experimental isolation of each AD-related transgene, it was determined that expression of the PS1M146V transgene product is responsible for the loss of the TNF-α effect on IP3R-mediated Ca2+ release. Furthermore, it was determined that the suppression of TNF-α receptor expression occurred in the presence of the presenilin transgene. Our findings attribute this familial AD mutation to suppressing a Ca2+-regulated signal cascade potentially intended to “inform” neurons of proximal neuroinflammatory events and trigger compensatory responses for protection of neural transmission.
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影响因子：
4.8
作者：
Park, Keigan M.;Yule, David I.;Bowers, William J.
通讯作者：
Bowers, William J.
影响因子：
6
作者：
Podlesniy, Petar;Kichev, Anton;Espinet, Carme
通讯作者：
Espinet, Carme
影响因子：
5.3
作者：
Ogoshi, F;Yin, HZ;Weiss, JH
通讯作者：
Weiss, JH
影响因子：
4.8
作者：
Zampieri, N;Xu, CF;Chao, MV
通讯作者：
Chao, MV
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影响因子：
9.3
作者：
Janelsins, Michelle C.;Mastrangelo, Michael A.;Oddo, Salvatore;LaFerla, Frank M.;Federoff, Howard J.;Bowers, William J.
通讯作者：
Bowers, William J.