Molecular mechanisms of neuroprotection: The interplay of Klotho, SIRT-1, Nrf2, and HO-1 in neurological health

Abstract

Neurological disorders significantly impair neuronal function and lead to cognitive and motor deficits. This review manuscript explores the therapeutic potential of key proteins-Klotho, SIRT-1, Nrf2, and HO-1-in combating these disorders. Neurological conditions encompass neurotraumatic, neurodegenerative, and neuropsychiatric diseases, all characterized by neuronal loss and dysfunction. The complex functions of Klotho, an anti-aging protein, and SIRT-1, a histone deacetylase, highlight their roles in neuronal survival and neuroprotection through the enhancement of antioxidant defences and the modulation of stress responses. Nrf2 functions as the principal regulator of the antioxidant response, whereas HO-1 facilitates the control of oxidative stress and the resolution of inflammation. Evidence suggests that the interplay between these proteins facilitates neuroprotection by decreasing oxidative damage and promoting cognitive function. The study emphasises the significance of signalling pathways, particularly the Nrf2/HO-1 axis, which are essential in mitigating oxidative stress and inflammation linked to neurodegenerative disorders. Future therapeutic strategies must consider personalized approaches, innovative drug delivery systems, and early intervention to optimize outcomes. This review provides a comprehensive framework for understanding how targeting these pathways can mitigate the burden of neurological disorders, advancing the development of effective interventions for enhancing brain health.

Keywords: Cellular Signaling; Klotho/SIRT-1/Nrf2/HO-1; Neurological disorders; Neuroprotection; Therapeutic strategies.