Gupta Sumedha, Gupta Abhishek Kumar, Mehan Sidharth, Khan Zuber, Gupta Ghanshyam Das, Narula Acharan S
Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab 144603, India.
Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab 144603, India. Electronic address: https://mehanneuroscience.org.
Neuroscience. 2025 Mar 17;569:331-353. doi: 10.1016/j.neuroscience.2025.01.021. Epub 2025 Jan 12.
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.
神经疾病对中枢神经系统有显著影响，在全球范围内导致日益严重的公共卫生危机。这些疾病的范围包括神经发育和神经退行性疾病。本文综述了细胞信号通路在这些疾病病理生理学中的关键作用，主要聚焦于谷氨酰胺酶/谷氨酸/NMDA受体信号通路，以及丝裂原活化蛋白激酶（MAPK）通路——细胞外信号调节激酶1/2（ERK1/2）、C-Jun氨基末端激酶（C-JNK）和p38丝裂原活化蛋白激酶（P38 MAPK）。这些通路的激活通常与神经元兴奋性毒性、细胞凋亡和炎症相关，导致许多其他病理状况，如创伤性脑损伤、中风和脑肿瘤。谷氨酸过度刺激与MAPK信号之间的相互作用加剧了神经退行性过程，凸显了细胞通讯在维持神经元健康方面的复杂性。信号功能失调会改变突触可塑性和神经元存活，导致各种神经疾病中的认知障碍。本文强调了针对这些信号通路进行治疗干预的潜力，促进神经保护并减轻神经炎症。结合精准医学和创新药物递送系统的见解可以提高治疗效果。总体而言，了解这些通路的复杂机制对于制定有效的策略以减轻神经疾病的影响并改善患者预后至关重要。本综述强调了进一步探索这些信号级联以促进治疗方法进展的必要性，确保为受神经疾病影响的个体带来更好的预后。
