Inhibition of ferroptosis through regulating neuronal calcium homeostasis: An emerging therapeutic target for Alzheimer?s disease

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, generates a serious threat to the health of the elderly. The AD brain is microscopically characterized by amyloid plaques and neurofibrillary tangles. There are still no effective therapeutic drugs to restrain the progression of AD though much attention has been paid to exploit AD treatments. Ferroptosis, a type of programmed cell death, has been reported to promote the pathological occurrence and development of AD, and inhibition of neuronal ferroptosis can effectively improve the cognitive impairment of AD. Studies have shown that calcium (Ca2+) dyshomeostasis is closely related to the pathology of AD, and can drive the occurrence of ferroptosis through several pathways, such interacting with iron, and regulating the crosstalk between endoplasmic reticulum (ER) and mitochondria. This paper mainly reviews the roles of ferroptosis and Ca2+ in the pathology of AD, and highlights that restraining ferroptosis through maintaining the homeostasis of Ca2+ may be an innovative target for the treatment of AD.

Automated summary

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, poses a serious threat to the health of the elderly. The microscopic features of the AD brain are amyloid plaques and neurofibrillary tangles. Despite extensive research, there are still no effective drugs to halt the progression of AD. Ferroptosis, a type of programmed cell death, has been shown to promote the development of AD, and inhibiting neuronal ferroptosis can improve cognitive impairment. Calcium (Ca2+) dyshomeostasis has been found to be closely related to AD pathology, driving ferroptosis through various pathways. This paper reviews the roles of ferroptosis and Ca2+ in AD pathology and suggests that targeting the homeostasis of Ca2+ to restrain ferroptosis may be an innovative approach for AD treatment.