Agarwood as a potential therapeutic for Alzheimer's disease: Mechanistic insights and target identification

Drug Discov Ther. 2024 Dec 21. doi: 10.5582/ddt.2024.01085. Online ahead of print.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairments. Despite extensive research, its pathogenesis remains incompletely understood, and effective treatments are limited. This study explored the therapeutic potential of agarwood in AD by integrating network pharmacology, protein-protein interaction (PPI) network analysis, and single-cell expression analysis. The results revealed that agarwood compounds may modulate key inflammatory genes such as NFKB1, STAT1, and TLR4, alleviating neuroinflammation; enhance the expression of HSP90 and regulate KDR signaling to improve blood-brain barrier (BBB) integrity; and promote the activity of PTPN11 and CXCR4 to support oligodendrocyte precursor cell (OPC) repair and remyelination. Single-cell expression analysis highlighted cell-type-specific expression patterns, particularly in OPCs and endothelial cells, underscoring their relevance in AD pathology. Agarwood's multi-dimensional therapeutic potential positions it as a promising candidate for the development of novel AD treatments.

Keywords: Alzheimer's disease; agarwood; blood-brain barrier; network pharmacology; neuroinflammation; oligodendrocyte precursor cells.