Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Institute of National Importance, Bangalore, Karnataka, India.
Methods Mol Biol. 2024;2816:117-128. doi: 10.1007/978-1-0716-3902-3_11.
In Alzheimer's disease, the synaptic loss is prominent due to the accumulation of Amyloid βeta (Aβ) protein in synapses, which affect neurotransmission, and thus ultimately causes neuronal loss. Tau, a microtubule-associated protein, is a vital protein of intracellular neurofibrillary tangles (NFTs) in AD. Along with the accumulation of aberrant proteins, glial cells, mainly astrocytes and microglia, play a major role in impairing neuronal network. Microglia have the ability to phagocytose Tau and rerelease in exosomes, which causes further spreading of Tau. Reduction in exosome synthesis can reduce spreading of Tau. Modulating microglia to clear the extracellular Tau seeds by its imported degradation would resolve the disease condition in Alzheimer's disease. In this study, we have shown the ability of α-linolenic acid (ALA) to inhibit the Tau aggregation and modulate their internalization property in microglial cells.
在阿尔茨海默病中，由于突触中β淀粉样蛋白（Aβ）的积累导致突触丢失明显，这会影响神经传递，最终导致神经元丢失。微管相关蛋白 tau 是阿尔茨海默病中细胞内神经原纤维缠结（NFT）的重要蛋白。随着异常蛋白的积累，胶质细胞，主要是星形胶质细胞和小胶质细胞，在损害神经网络方面起着主要作用。小胶质细胞具有吞噬 tau 并在外泌体中重新释放的能力，这导致 tau 的进一步扩散。减少外泌体的合成可以减少 tau 的扩散。通过导入降解来调节小胶质细胞清除细胞外 tau 种子可以解决阿尔茨海默病中的疾病状况。在这项研究中，我们已经表明α-亚麻酸（ALA）能够抑制 tau 聚集，并调节其在小胶质细胞中的内化特性。
