VDAC1型
粒体自噬
生物
转基因小鼠
τ蛋白
细胞生物学
自噬
转基因
线粒体
神经科学
内科学
阿尔茨海默病
生物化学
医学
细胞凋亡
大肠杆菌
细菌外膜
基因
疾病
作者
Murali Vijayan,Rainier Vladlen Alvir,Razelle Alvir,Lloyd E Bunquin,Jangampalli Adi Pradeepkiran,P. Hemachandra Reddy
出处
期刊:Aging Cell
[Wiley]
日期:2022-07-07
卷期号:21 (8)
被引量:7
摘要
Abstract Alzheimer's disease (AD) is the most common cause of mental dementia in the aged population. AD is characterized by the progressive decline of memory and multiple cognitive functions, and changes in behavior and personality. Recent research has revealed age‐dependent increased levels of VDAC1 in postmortem AD brains and cerebral cortices of APP, APPxPS1, and 3xAD.Tg mice. Further, we found abnormal interaction between VDAC1 and P‐Tau in the AD brains, leading to mitochondrial structural and functional defects. Our current study aimed to understand the impact of a partial reduction of voltage‐dependent anion channel 1 (VDAC1) protein on mitophagy/autophagy, mitochondrial and synaptic activities, and behavior changes in transgenic TAU mice in Alzheimer's disease. To determine if a partial reduction of VDAC1 reduces mitochondrial and synaptic toxicities in transgenic Tau (P301L) mice, we crossed heterozygote VDAC1 knockout (VDAC1 +/− ) mice with TAU mice and generated double mutant (VDAC1 +/− /TAU) mice. We assessed phenotypic behavior, protein levels of mitophagy, autophagy, synaptic, other key proteins, mitochondrial morphology, and dendritic spines in TAU mice relative to double mutant mice. Partial reduction of VDAC1 rescued the TAU‐induced behavioral impairments such as motor coordination and exploratory behavioral changes, and learning and spatial memory impairments in VDAC1 +/− /TAU mice. Protein levels of mitophagy, autophagy, and synaptic proteins were significantly increased in double mutant mice compared with TAU mice. In addition, dendritic spines were significantly increased; the mitochondrial number was significantly reduced, and mitochondrial length was increased in double mutant mice. Based on these observations, we conclude that reduced VDAC1 is beneficial in symptomatic‐transgenic TAU mice.
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