Kelch-like ECH-associated Protein 1-nuclear Factor Erythroid 2-related Factor 2 Pathway Activation in Neuroprotection and Cognitive Enhancement

Abstract

Neurodegenerative diseases and cognitive decline pose significant global health challenges. The Kelch-like ECH-associated protein 1 (Keap1) – nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a master regulator of cellular defense against oxidative stress and inflammation, factors implicated in these conditions. This review examines the pivotal role of Keap1-Nrf2 pathway activation in promoting neuroprotection and cognitive enhancement. A comprehensive literature search was conducted across databases such as PubMed, Scopus, and Web of Science. Studies investigating direct activation of the Keap1-Nrf2 pathway, its downstream targets, and its impact on neuronal health and cognitive function were included. Activation of the Keap1-Nrf2 pathway leads to the transcription of antioxidant and cytoprotective genes, mitigating neuronal damage caused by reactive oxygen species and inflammatory mediators. Studies demonstrate that enhanced Nrf2 activity can protect against insults in models of Alzheimer's disease, Parkinson's disease, and stroke, improving neuronal survival and reducing neuroinflammation. Furthermore, this pathway positively influences synaptic plasticity and memory formation. The Keap1-Nrf2 pathway's robust antioxidant and anti-inflammatory actions position it as a promising therapeutic target. Strategies aimed at inhibiting Keap1 or directly activating Nrf2 show significant potential for ameliorating neurodegenerative processes and improving cognitive function. Activating the Keap1-Nrf2 pathway represents a compelling therapeutic strategy for neuroprotection and cognitive enhancement, offering a promising avenue for combating debilitating neurological disorders.