Exosomes are nano-sized extracellular vesicles that perform a variety of biological functions linked to the pathogenesis of various neurodegenerative disorders. In Alzheimer's disease (AD), for examples, exosomes are responsible for the release of Aβ oligomers, and their extracellular accumulation, although the underpinning molecular machinery remains elusive. We propose a novel model for Alzheimer's Aβ accumulation based on Ca²⁺-dependent exosome release from astrocytes. Moreover, we exploit our model to assess how temperature dependence of exosome release could interact with Aβ neurotoxicity. We predict that voltage-gated Ca²⁺ channels (VGCCs) along with the transient-receptor potential M8 (TRPM8) channel are crucial molecular components in Alzheimer's progression.

外泌体是纳米级的细胞外囊泡，具有与各种神经退行性疾病发病机制相关的多种生物学功能。例如，在阿尔茨海默病 (AD) 中，外泌体负责释放β寡聚体及其细胞外积累，尽管支撑分子机制仍然难以捉摸。我们提出了一种新的阿尔茨海默氏症模型β 累积基于 钙从星形胶质细胞中释放²⁺依赖性外泌体。此外，我们利用我们的模型来评估外泌体释放的温度依赖性如何与β神经毒性。我们预测电压门控钙²⁺通道 (VGCC) 以及瞬时受体电位 M8 (TRPM8) 通道是阿尔茨海默病进展的关键分子成分。