Protein homeostasis is essential for the wellbeing of several cellular systems. Post-translational modifications (PTM) coordinate various pathways in response to abnormal aggregation of proteins in neurodegenerative disease states. In the presence of accumulating misfolded proteins and toxic aggregates, the small ubiquitin-like modifier (SUMO) is associated with various substrates, including chaperones and other recruited factors, for refolding and for clearance via proteolytic systems, such as the ubiquitin-proteasome pathway (UPS), chaperone-mediated autophagy (CMA) and macroautophagy. However, these pathological aggregates are also known to inhibit both the UPS and CMA, further creating a toxic burden on cells. This review suggests that re-routing cytotoxic aggregates towards selective macroautophagy by modulating the SUMO pathway could provide new mechanisms towards neuroprotection.

蛋白质稳态对于多个细胞系统的健康至关重要。翻译后修饰（PTM）协调各种途径，以响应神经退行性疾病状态下蛋白质的异常聚集。在累积错误折叠的蛋白质和毒性聚集物的存在，所述š商场ù biquitin状莫difier（SUMO）与各种底物（包括分子伴侣和其他募集的因子）相关联，以通过蛋白水解系统（如泛素-蛋白酶体途径（UPS），分子伴侣介导的自噬（CMA）和宏观自噬）进行复性和清除。然而，还已知这些病理性聚集体抑制UPS和CMA，从而进一步对细胞产生毒性负担。这项审查表明，通过调节SUMO途径将细胞毒性聚集体重新定向至选择性的巨噬细胞吞噬，可能会提供新的神经保护机制。