Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis.
Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis.
复制标题
DOI：
10.1002/alz.12610
复制
发表时间：
2022-11
影响因子：
14
通讯作者：
Greig, Nigel H.
中科院分区：
文献类型：
--
作者：
Lecca, Daniela;Jung, Yoo Jin;Scerba, Michael T.;Hwang, Inho;Kim, Yu Kyung;Kim, Sun;Modrow, Sydney;Tweedie, David;Hsueh, Shih-Chang;Liu, Dong;Luo, Weiming;Glotfelty, Elliot;Li, Yazhou;Wang, Jia-Yi;Luo, Yu;Hoffer, Barry J.;Kim, Dong Seok;McDevitt, Ross A.;Greig, Nigel H.
关键词：
评估3，6‘-二硫代泊马度胺对5xFAD阿尔茨海默病(AD)小鼠的疗效，以验证神经炎症直接参与突触/神经元丢失和认知功能下降的假设。淀粉样蛋白-β(A-β)或以tau为重点的临床试验已被证明在缓解AD相关的认知障碍方面不成功。需要确定新的药物靶点。神经炎症是神经退行性疾病的治疗靶点，而肿瘤坏死因子-α是神经炎症的关键驱动因素。AD相关的慢性神经炎直接导致进行性突触/神经元丢失和认知功能下降。在不改变β生成的情况下，从药物上减轻小胶质细胞/星形胶质细胞的激活将确定神经炎症在AD进展中的作用。降低肿瘤坏死因子-α的化合物到达大脑的困难，以及确定保护神经炎性过程的有益作用的治疗时间窗口。小胶质细胞/星形胶质细胞与健康脑内突触可塑性/功能的维持密切相关，并被Aβ干扰。慢性胶质细胞增多症的缓解可以恢复突触的稳态/认知功能。
Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline. Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful in mitigating AD‐associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF‐α a pivotal neuroinflammatory driver. AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression. Difficulty of TNF‐α‐lowering compounds reaching brain, and identification of a therapeutic‐time window to preserve the beneficial role of neuroinflammatory processes. Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.
登录
查看更多内容
影响因子：
4.6
作者：
Davis BM;Salinas-Navarro M;Cordeiro MF;Moons L;De Groef L
通讯作者：
De Groef L
影响因子：
3
作者：
Andoh M;Koyama R
通讯作者：
Koyama R
影响因子：
4.3
作者：
Jung YJ;Tweedie D;Scerba MT;Kim DS;Palmas MF;Pisanu A;Carta AR;Greig NH
通讯作者：
Greig NH
影响因子：
11.5
作者：
Holstein SA;McCarthy PL
通讯作者：
McCarthy PL
影响因子：
5.6
作者：
Huang PS;Tsai PY;Yang LY;Lecca D;Luo W;Kim DS;Hoffer BJ;Chiang YH;Greig NH;Wang JY
通讯作者：
Wang JY