Chaperones and cellular degradative mechanisms modulate Tau aggregation. During aging and neurodegenerative disorders, the cellular proteostasis is disturbed due to impaired protective mechanisms. This results in accumulation of aberrant Tau aggregates in the neuron that leads to microtubule destabilization and neuronal degeneration. The intricate mechanisms to prevent Tau aggregation involve chaperones, autophagy, and proteasomal system have gained main focus about concerning to therapeutic intervention. However, the thorough understanding of other key proteins, such as Valosin-containing protein (VCP), is limited. In various neurodegenerative diseases, the chaperone-like activity of VCP is involved in preventing protein aggregation and mediating the degradation of aberrant proteins by proteasome and autophagy. In the case of Tau aggregation associated with Alzheimer’s disease, the importance of VCP is poorly understood. VCP is known to co-localize with Tau, and alterations in VCP cause aberrant accumulation of Tau. Nevertheless, the direct mechanism of VCP in altering Tau aggregation is not known. Hence, we speculate that VCP might be one of the key modulators in preventing Tau aggregation and can disintegrate Tau aggregates by directing its clearance by autophagy.

分子伴侣和细胞降解机制调节 Tau 聚集。在衰老和神经退行性疾病期间，由于保护机制受损，细胞蛋白质稳态受到干扰。这导致异常 Tau 聚集体在神经元中的积累，从而导致微管不稳定和神经元变性。防止 Tau 聚集的复杂机制涉及分子伴侣、自噬和蛋白酶体系统，已成为治疗干预的主要焦点。然而，对其他关键蛋白质，如含 Valosin 的蛋白质 (VCP) 的透彻了解是有限的。在各种神经退行性疾病中，VCP 的分子伴侣样活性参与阻止蛋白质聚集和介导蛋白酶体和自噬对异常蛋白质的降解。在与阿尔茨海默病相关的 Tau 聚集的情况下，人们对 VCP 的重要性知之甚少。已知 VCP 与 Tau 共定位，并且 VCP 的改变导致 Tau 的异常积累。然而，VCP 改变 Tau 聚集的直接机制尚不清楚。因此，我们推测 VCP 可能是阻止 Tau 聚集的关键调节剂之一，并且可以通过引导自噬清除 Tau 聚集体来分解 Tau 聚集体。