Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review

Abstract

Developmental signalling pathways such as Wnt/β-catenin, Notch and Sonic hedgehog play a central role in nearly all the stages of neuronal development. The term ‘embryonic’ might appear to be a misnomer to several people because these pathways are functional during the early stages of embryonic development and adulthood, albeit to a certain degree. Therefore, any aberration in these pathways or their associated components may contribute towards a detrimental outcome in the form of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke. In the last decade, researchers have extensively studied these pathways to decipher disease-related interactions, which can be used as therapeutic targets to improve outcomes in patients with neurological abnormalities. However, a lot remains to be understood in this domain. Nevertheless, there is strong evidence supporting the fact that embryonic signalling is indeed a crucial mechanism as is manifested by its role in driving memory loss, motor impairments and many other processes after brain trauma. In this review, we explore the key roles of three embryonic pathways in modulating a range of homeostatic processes such as maintaining blood–brain barrier integrity, mitochondrial dynamics and neuroinflammation. In addition, we extensively investigated the effect of these pathways in driving the pathophysiology of a range of disorders such as Alzheimer's, Parkinson's and diabetic neuropathy. The concluding section of the review is dedicated to neurotherapeutics, wherein we identify and list a range of biological molecules and compounds that have shown enormous potential in improving prognosis in patients with these disorders.

Keywords

• Wnt/β-catenin
• Notch
• Sonic hedgehog
• CNS
• neurodegeneration
• neurotherapeutics