Gladstone Institutes, San Francisco, CA, USA.
Helen and Robert Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Adv Exp Med Biol. 2019;1184:47-55. doi: 10.1007/978-981-32-9358-8_4.
Multiple neurodegenerative conditions including Alzheimer's disease and frontotemporal dementia are characterized by the accumulation of tau in the brain, associated with synapse loss and cognitive decline. Currently, the molecular events that lead to tau aggregation, and the pathological effects of the tau protein, are incompletely understood. Recent work has highlighted aberrant acetylation of tau as a key to understanding the pathophysiological roles of this protein. Specific acetylation sites regulate the formation of tau aggregates, synaptic signaling and long-term potentiation. Unraveling the details of this emerging story may offer novel insights into potential therapeutic approaches for devastating neurodegenerative diseases.
多种神经退行性疾病,包括阿尔茨海默病和额颞叶痴呆,其特征是脑中tau 的积累,与突触丧失和认知能力下降有关。目前,导致 tau 聚集的分子事件以及 tau 蛋白的病理作用尚不完全清楚。最近的研究强调了 tau 的异常乙酰化是理解该蛋白病理生理作用的关键。特定的乙酰化位点调节 tau 聚集、突触信号传递和长时程增强的形成。揭示这一新兴故事的细节可能为毁灭性神经退行性疾病的潜在治疗方法提供新的见解。