Fig. 5: Therapeutic candidates targeting LDs in microglia.
From: Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases
This figure summarizes the molecular mechanisms governing LDs biogenesis and degradation, highlighting potential therapeutic targets and modulators. LDs degradation occurs via two major pathways: lipolysis and lipophagy. Lipolysis is mediated by ATGL, HSL, and MGL, sequentially hydrolyzing TAG into free fatty acids (FFAs) and monoacylglycerol. Lipophagy involves the engulfment of LDs by autophagosomes (LC3-associated) and subsequent degradation in lysosomes. Therapeutic interventions can target these pathways. Inhibitors of LDs formation include DGAT and ACAT inhibitors (e.g., CP-113,818), perilipin modulators, and ACSL inhibitors (e.g., Triacsin C). In contrast, enhancing LDs degradation can be achieved through lipolysis inducers, perilipin regulators, or lipophagy enhancers such as metformin, resveratrol, rapamycin, and TFEB activators. These strategies offer potential to restore cellular lipid homeostasis and improve microglial function in neurodegenerative diseases. Created with Biorender.com.
