Fig. 3: LD dynamics in neurodegenerative diseases (AD, PD, ALS).
From: Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases
Schematic of pathways proposed to promote microglial lipid-droplets (LDs) accumulation. AD: risk genes (TREM2, SREBP2, APOE4, ABCA1/7, PICALM, LRP1) disrupt lipid homeostasis; Aβ/ER stress drive DGAT2-dependent FFA → TAG conversion; neurons transfer lipids to microglia via TREM2/CD36. PD: neuronal α-syn aggregates transfer to microglia (e.g., via tunneling nanotubes); LDs-bound α-syn is linked to reduced phagocytosis and increased oxidative stress; lipolysis may further modulate toxicity. ALS: neuronal mitochondrial defects and astrocytic LDs remodeling (e.g., SOD1G93A, PDK2 silencing) increase lipid flux; mutations (VAPB/ALS8, SPG11) and DGAT2/TDP-43 dysregulation associate with altered LDs metabolism. Central cell depicts a microglion with increased LDs load. Solid arrows indicate reported interactions; dashed arrows denote inferred links. Created with Biorender.com.
