Molecular Crosstalk in Neurodegeneration: Pathways, Gene Expression Dynamics, and Natural Therapeutics

Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis present a growing global health challenge due to their complex and multifactorial pathogenesis.Central to these disorders is the molecular crosstalk among proteostatic, immune, genetic, and metabolic pathways, where dysregulation amplifies neuronal damage and accelerates disease progression.This review synthesizes recent insights into the breakdown of proteostasis, mitochondrial dysfunction, oxidative stress, and neuroinflammation, highlighting their interconnected roles in neurodegeneration.Advances in multi-omics technologies and gene expression profiling provide robust platforms for identifying disease-specific biomarkers and mechanistic signatures, while artificial intelligence and machine learning accelerate data integration, biomarker discovery, and personalized therapeutic development.Special emphasis is placed on the neuroprotective potential of phytochemicals and bioactive natural compounds, which demonstrate antioxidant, anti-inflammatory, and neurotrophic effects that often surpass single-target synthetic drugs.By integrating computational approaches with natural therapeutics, this work underscores a paradigm shift toward holistic, personalized, and multi-targeted strategies for the prevention and management of neurodegenerative diseases.