Disruptions in cellular communication: Molecular interplay between glutamate/NMDA signalling and MAPK pathways in neurological disorders.

Abstract

Neurological disorders significantly impact the central nervous system, contributing to a growing public health crisis globally. The spectrum of these disorders includes neurodevelopmental and neurodegenerative diseases. This manuscript reviews the crucial roles of cellular signalling pathways in the pathophysiology of these conditions, focusing primarily on glutaminase/glutamate/NMDA receptor signalling, alongside the mitogen-activated protein kinase (MAPK) pathways-ERK1/2, C-JNK, and P38 MAPK. Activation of these pathways is often correlated with neuronal excitotoxicity, apoptosis, and inflammation, leading to many other pathological conditions such as traumatic brain injury, stroke, and brain tumor. The interplay between glutamate overstimulation and MAPK signalling exacerbates neurodegenerative processes, underscoring the complexity of cellular communication in maintaining neuronal health. Dysfunctional signalling alters synaptic plasticity and neuronal survival, contributing to cognitive impairments in various neurological diseases. The manuscript emphasizes the potential of targeting these signalling pathways for therapeutic interventions, promoting neuroprotection and reducing neuroinflammation. Incorporating insights from precision medicine and innovative drug delivery systems could enhance treatment efficacy. Overall, understanding the intricate mechanisms of these pathways is essential for developing effective strategies to mitigate the impact of neurological disorders and improve patient outcomes. This review highlights the necessity for further exploration into these signalling cascades to facilitate advancements in therapeutic approaches, ensuring better prognoses for individuals affected by neurological conditions.