MPTP公司
线粒体通透性转换孔
神经退行性变
神经科学
线粒体
氧化应激
阿尔茨海默病
调解人
生物
细胞生物学
医学
疾病
细胞凋亡
病理
程序性细胞死亡
内分泌学
生物化学
多巴胺
多巴胺能
作者
Rodrigo A Quntanilla,Carola Tapia-Monsalves
出处
期刊:Current Neuropharmacology
[Bentham Science]
日期:2020-11-09
卷期号:18 (11): 1076-1091
被引量:22
标识
DOI:10.2174/1570159x18666200525020259
摘要
Accumulative evidence has shown that mitochondrial dysfunction plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial impairment actively contributes to the synaptic and cognitive failure that characterizes AD. The presence of soluble pathological forms of tau like hyperphosphorylated at Ser396 and Ser404 and cleaved at Asp421 by caspase 3, negatively impacts mitochondrial bioenergetics, transport, and morphology in neurons. These adverse effects against mitochondria health will contribute to the synaptic impairment and cognitive decline in AD. Current studies suggest that mitochondrial failure induced by pathological tau forms is likely the result of the opening of the mitochondrial permeability transition pore (mPTP). mPTP is a mitochondrial mega-channel that is activated by increases in calcium and is associated with mitochondrial stress and apoptosis. This structure is composed of different proteins, where Ciclophilin D (CypD) is considered to be the primary mediator of mPTP activation. Also, new studies suggest that mPTP contributes to Aβ pathology and oxidative stress in AD. Further, inhibition of mPTP through the reduction of CypD expression prevents cognitive and synaptic impairment in AD mouse models. More importantly, tau protein contributes to the physiological regulation of mitochondria through the opening/interaction with mPTP in hippocampal neurons. Therefore, in this paper, we will discuss evidence that suggests an important role of pathological forms of tau against mitochondrial health. Also, we will discuss the possible role of mPTP in the mitochondrial impairment produced by the presence of tau pathology and its impact on synaptic function present in AD.
科研通智能强力驱动
Strongly Powered by AbleSci AI