Current perspectives on the genetics of neurodegenerative diseases: A narrative review

Neurodegenerative disorders are a growing global health risk because of their progressive and incurable nature. Although distinct, most of these neurodegenerative disorders share similar pathological hallmarks, including progressive neuronal loss and cognitive decline, which are further driven by environmental and/or genetic factors. This review provides a detailed exploration of the driving factors, epidemiological trends, pathophysiology, and existing and upcoming therapeutic strategies for some of the most reported neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. The data were combined through a search that spanned various scientific databases to identify peer-reviewed original research articles, meta-analyses, cohort studies, and review papers using specific keywords in different combinations to gather epidemiological, pathophysiological, and therapeutic data for each neurodegenerative disorder, which were then combined to perform a comprehensive review. Apart from the conventional pathological hallmarks, this review also elucidates some mechanisms that have been shown only recently to be involved in the onset and progression of neurodegenerative disorders. These mechanisms include the gut–brain axis, delving into the intricacies of how changes in the gut microbiome of individuals contribute to the onset and rapid progression of neurodegenerative disorders. Moreover, the review addresses the recent surge in reports suggesting that diseases such as type 2 diabetes mellitus or coronavirus disease of 2019 actually increase the risk of onset of these neurodegenerative disorders. The future ultimately calls for a multifaceted strategy that integrates customized treatment and molecular insights to address root causes as well as symptoms. To develop revolutionary treatments for these crippling conditions, a better understanding of neuroimmune regulation, cognitive resilience, and genetic–environment interactions is needed.