ER stress and UPR in Alzheimer's disease: mechanisms, pathogenesis, treatments

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of A beta to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the unique role of ER stress in AD pathogenesis, reviewing key findings, and existing controversy in an attempt to summarize plausible therapeutic interventions in the management of AD pathophysiology.

Automated summary

Alzheimer's disease is a neurodegenerative disorder that causes memory and cognitive function loss, which is a burden on the healthcare system worldwide. Current therapies for Alzheimer's disease are still being developed. In addition to the toxic forms of A beta, further research should focus on the role of endoplasmic reticulum stress in Alzheimer's disease.