神经退行性变
神经科学
高磷酸化
磷酸化
机制(生物学)
陶氏病
Tau病理学
轴浆运输
葛兰素史克-3
τ蛋白
蛋白酶体
炎症
细胞生物学
生物
化学
阿尔茨海默病
疾病
医学
病理
哲学
免疫学
认识论
作者
Mathew Blurton-Jones,Frank M. LaFerla
标识
DOI:10.2174/156720506779025242
摘要
Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Aβ) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Aβ may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Aβ can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Aβ may facilitate the development of tau pathology. A great deal of work suggests that Aβ may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Aβ may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Aβ also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Aβ may inhibit tau degradation via the proteasome. Lastly, Aβ and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Aβ and tau, thereby leading to the development of AD neurodegeneration. Keywords: Phosphorylation, inflammation, proteasome, axonal transport, neurofibrillary tangles, PHF, oligomer, amyloid
科研通智能强力驱动
Strongly Powered by AbleSci AI