Investigation of Autophagy and Apoptosis Pathways in Neuronal Cells Using Molecular and Bioinformatics Tools

https://doi.org/10.5281/zenodo.19659847

Abstract

Autophagy and apoptosis are two interconnected cellular processes that play critical roles in maintaining neuronal homeostasis, particularly in post-mitotic neurons with limited regenerative capacity. Autophagy acts as a pro-survival mechanism by degrading damaged organelles and protein aggregates through a lysosome-dependent pathway involving the ULK1 complex, Beclin-1/Vps34 nucleation, LC3 lipidation, and autophagosome-lysosome fusion. In contrast, apoptosis serves as a programmed cell death pathway, executed primarily through the intrinsic (mitochondrial, Bcl-2 family-regulated) and extrinsic (death receptor-mediated) routes, culminating in caspase activation and orderly cellular dismantling. These pathways exhibit extensive crosstalk, with shared regulators such as Beclin-1 (inhibited by Bcl-2 under normal conditions but released during stress) and caspases that can cleave Beclin-1 to shift the balance toward death. In neurons, selective autophagy forms like mitophagy (PINK1/Parkin pathway) and aggrephagy are essential for quality control, while dysregulation contributes to neurodegenerative diseases including Alzheimer’s and Parkinson’s. Molecular tools (tandem fluorescent LC3, Cyto-ID) and bioinformatics approaches (STRING, Cytoscape, KEGG, WGCNA) combined with machine learning enable systematic mapping of pathway interactions, identification of hub genes, and prediction of therapeutic targets. Understanding this dynamic balance offers promising avenues for neuroprotective interventions in neurological disorders.