Molecular insight into the crosstalk of UPS components and Alzheimer’s disease

The ubiquitin (Ub)-proteasome system (UPS) targets various cellular proteins for degra-dation. It has been found that defects in the UPS play a crucial role in the pathogenesis of Alzheimer's disease (AD), as the existence of Ub immunoreactivity in AD-linked neuronal inclu-sions, including neurofibrillary tangles, is observed in all types of AD cases. Current investigations have shown that components of the UPS can be connected with the early stage of AD, which is characterized by synaptic dysfunction, and to the late phases of the disease, marked by neurodegen-eration. Although the significance of UPS in the pathogenesis of AD has been emphasized, targeted treatment at the main components of these pathways has a great perspective in advancing new therapeutic interventions for AD. In this review, we emphasize the relationship between UPS and AD pathology. We also represent the recent therapeutic advancements targeting UPS components in AD.