BIOCHEMICAL PATHWAYS IN NEURODEGENERATIVE DISORDERS: A MOLECULAR PERSPECTIVE

Abstract

Neurodegenerative disorders involve progressive neuronal dysfunction driven by complex molecular changes. Alzheimer’s disease and Parkinson’s disease differ clinically and anatomically, yet both are associated with mitochondrial impairment, lipid dysregulation, inflammatory signaling, and cellular stress. This study aimed to identify disease-specific and shared biochemical pathways in Alzheimer’s disease and Parkinson’s disease using comparative transcriptomic analysis. Publicly available human microarray datasets from Alzheimer’s disease hippocampal tissue and Parkinson’s disease substantia nigra neurons were analyzed. Expression data were log2 transformed, quality assessed, and examined using principal component analysis. Differentially expressed genes were identified using Welch’s t-test with false discovery rate correction. Shared genes were annotated and evaluated through Gene Ontology biological process and KEGG pathway enrichment analyses. Alzheimer’s disease showed predominant downregulation of genes associated with neuronal signalling and metabolic regulation, whereas Parkinson’s disease displayed stronger transcriptomic activation. Comparative analysis identified 57 shared differentially expressed probes, including genes linked to mitochondrial transport, lipid handling, phospholipid signaling, and cellular stress regulation. Enrichment analysis highlighted cholesterol homeostasis, fatty acid oxidation, mitochondrial protein import, PPAR signaling, HIF-1 signaling, cAMP signaling, autophagy, and glycerophospholipid metabolism as common pathway-level disturbances. The findings indicate that Alzheimer’s disease and Parkinson’s disease share convergent molecular mechanisms involving mitochondrial dysfunction, lipid metabolism, inflammatory signaling, and cellular stress responses. These pathway-level alterations may provide useful targets for future biomarker and therapeutic investigations.