LAMP2-Centered Autophagy Network and HDAC Inhibitors as Therapeutic Leads in Alzheimer’s and Parkinson’s Diseases: A Bioinformatic Analysis
Year: 2026
Type: article
Abstract: Among neurodegenerative disorders, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most commonly diagnosed, and both present with distinct proteinopathies and progressive neuronal loss. Studies have implicated autophagy dysfunction as a common mechanism in both diseases. Therefore, the primary objective of our study is to use bioinformatics techniques to identify commonly upregulated genes associated with autophagy and apoptosis in AD and PD and to develop novel therapeutic agents targeting these genes. Using publicly available transcriptomic data (GSE5281 and GSE48350 for AD; GSE49036 for PD), differentially expressed genes (DEGs) are identified and restricted to autophagy and apoptosis related genes compiled from the Human Autophagy Database. According to our results, the genes CARD8, FXN, LAMP2, EVI2B, MYOT, P2RX7, and MEGF10 are consistently upregulated in both conditions, while ELAPOR1 is downregulated. Our PPI network analysis results highlight LAMP2 as a central molecule regulating lysosomal-autophagic fusion. Gene enrichment analyses implicate pathways involved in autophagy, lysosomal activity, and inflammation. Drug repurposing analysis using the DSigDB database on the Enrichr platform has shown that the histone deacetylase (HDAC) inhibitors Vorinostat (suberoylanilide hydroxamic acid, SAHA), Trichostatin A (TSA), and Valproic Acid (VPA) stand out as promising agents that may regulate this common gene network. These findings provide a number of autophagy- and apoptosis-related targets and therapies with the potential to address shared pathological features of AD and PD.
DOI: 10.7240/jeps.1758216
Institution: İzmir University of Economics
Language: Turkish
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Award: G1321993874
OpenAlex ID: W7139917160