Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder

• Main Authors: Pei Wang, Fang Wang, Lan Ni, Pengfei Wu, Jianguo Chen
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: Acta Pharmaceutica Sinica B
• Subjects: Reactive oxygen species; N-Methyl-d-aspartate receptor; Oxidative stress; Synaptic plasticity; Long-term potentiation; Cognitive disorder
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211383520308029

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity via altering functions of key proteins, such as N-methyl-d-aspartate receptor (NMDAR). Age-related cognitive disorders includes Alzheimer's disease (AD), vascular dementia (VD), and age-associated memory impairment (AAMI). Based on the critical role of NMDAR-dependent long-term potentiation (LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. In this review, we summarize the involvement of redox-altered plasticity in cognitive disorders by presenting the available evidence. According to reports from our laboratory and other groups, this “redox-altered plasticity” is more similar to functional changes rather than organic injuries, and strategies targeting redox-altered plasticity using pharmacological agents might reverse synaptic dysfunctions and memory abnormalities in the early stage of cognitive disorders. Targeting redox modifications for NMDARs may serve as a novel therapeutic strategy for memory deficits.