Molecular mechanism of caloric restriction mimetics-mediated neuroprotection of age-related neurodegenerative diseases: an emerging therapeutic approach

Aging-induced neurodegenerative diseases (NDs) are significantly increasing health problem worldwide. It has been well documented that oxidative stress is one of the potential causes of aging and age-related NDs. There are no drugs for the treatment of NDs, therefore there is an immediate necessity for the development of strategies/treatments either to prevent or cure age-related NDs. Caloric restriction (CR) and intermittent fasting have been considered as effective strategies in increasing the healthspan and lifespan, but it is difficult to adhere to these routines strictly, which has led to the development of calorie restriction mimetics (CRMs). CRMs are natural compounds that provide similar molecular and biochemical effects of CR, and activate autophagy process. CRMs have been reported to regulate redox signaling by enhancing the antioxidant defense systems through activation of the Nrf2 pathway, and inhibiting ROS generation through attenuation of mitochondrial dysfunction. Moreover, CRMs also regulate redox-sensitive signaling pathways such as the PI3K/Akt and MAPK pathways to promote neuronal cell survival. Here, we discuss the neuroprotective effects of various CRMs at molecular and cellular levels during aging of the brain. The CRMs are envisaged to become a cornerstone of the pharmaceutical arsenal against aging and age-related pathologies.

Automated summary

Aging-induced neurodegenerative diseases (NDs) are a growing health problem worldwide, and oxidative stress is considered a potential cause. Currently, there are no drugs available for the treatment of NDs, so it is necessary to develop strategies/treatments to prevent or cure these age-related diseases. Caloric restriction and intermittent fasting have shown positive effects on healthspan and lifespan, but strict adherence to these routines is difficult, leading to the development of calorie restriction mimetics (CRMs). CRMs are natural compounds that mimic the effects of caloric restriction and activate autophagy. They have been found to regulate redox signaling, enhance antioxidant defense systems, and inhibit ROS generation. Additionally, CRMs also promote neuronal cell survival by regulating redox-sensitive signaling pathways. This article discusses the neuroprotective effects of various CRMs at the molecular and cellular levels during brain aging, and highlights their potential as a cornerstone in the pharmaceutical arsenal against aging and age-related pathologies.