Jackson Noel A, Guerrero-Muñoz Marcos J, Castillo-Carranza Diana L
School of Public Health, Harvard University, Boston, MA, United States.
School of Medicine, University of Monterrey, San Pedro Garza García, Mexico.
Front Aging Neurosci. 2022 Aug 18;14:974414. doi: 10.3389/fnagi.2022.974414. eCollection 2022.
The conversion and transmission of misfolded proteins established the basis for the prion concept. Neurodegenerative diseases are considered "prion-like" disorders that lack infectivity. Among them, tauopathies are characterized by the conversion of native tau protein into an abnormally folded aggregate. During the progression of the disease, misfolded tau polymerizes into oligomers and intracellular neurofibrillary tangles (NFTs). While the toxicity of NFTs is an ongoing debate, the contribution of tau oligomers to early onset neurodegenerative pathogenesis is accepted. Tau oligomers are readily transferred from neuron to neuron propagating through the brain inducing neurodegeneration. Recently, transmission of tau oligomers exosomes is now proposed. There is still too much to uncover about tau misfolding and propagation. Here we summarize novel findings of tau oligomers transmission and propagation exosomes.
错误折叠蛋白的转化与传播奠定了朊病毒概念的基础。神经退行性疾病被认为是缺乏传染性的“类朊病毒”疾病。其中,tau蛋白病的特征是天然tau蛋白转化为异常折叠的聚集体。在疾病进展过程中,错误折叠的tau蛋白聚合成寡聚体和细胞内神经原纤维缠结(NFTs)。虽然NFTs的毒性仍存在争议,但tau寡聚体对早发性神经退行性疾病发病机制的作用已被认可。tau寡聚体很容易在神经元之间传递,通过大脑传播,诱导神经退行性变。最近,有人提出tau寡聚体可通过外泌体进行传递。关于tau蛋白的错误折叠和传播,仍有许多有待揭示的地方。在此,我们总结了tau寡聚体通过外泌体传递和传播的新发现。