Elucidate the nexus between sonic hedgehog, fibroblast growth factor, Wnt/beta signalling on regulatory kinases for CRMP2 in neurodegenerative disorders

Background Neurodegenerative disorders (NDD) are a heterogenous group of neurological conditions characterized by progressive neuronal loss that leads to neuronal death within the brain and spinal cord. This abrupt neuronal connection leads to the development of diverse neurodegenerative disorders. It includes dementia, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Pick’s Disease. Main Body Clinical manifestations of neurodegenerative diseases, including cognitive decline, motor dysfunction, and behavioral changes may occur before neuronal loss becomes evident. This correlation is complex as symptoms can appear prior to any specific type of neuronal loss, and some other factors such as inflammation can serve a potential role for the progression of neurological symptoms. Multiple triggering agents, including age, genetic, lifestyle, and environmental factors, contribute to establishing a habitat that is detrimental to neuron lifespan. Therefore, we may anticipate a startling number of instances in the near future. The main goal of this paper is to emphasize the fundamental molecular and cellular pathways that are primarily responsible for the pathophysiology of neurodegenerative disorders. We have conducted a comprehensive literature review of numerous databases, including PubMed, Google Scholar, and Research Gate, in order to accomplish this objective. Findings suggest that several signaling pathways regulate a variety of kinases, including Glycogen Synthase Kinase 3 Beta (GSK3β), Cyclin-dependent kinase 5 (CDK5), andRho-associated kinase (ROCK), which phosphorylate CRMP2 and impair neuronal polarity and axonal growth. Conclusion We hypothesize that inhibition of GSK3β and CDK5 may reduce hyperphosphorylation of CRMP2, which is regulated by kinase activity modulated by upstream signaling networks including the Wnt/β-catenin, Shh, FGF, and JAK/STAT. Clinical trial number Not applicable.