AI Article Synopsis

  • Dyslipidemia in the brain is linked to neurodegenerative diseases, but the specific molecular processes are not well understood.
  • PDZD8 is a protein that helps transport cholesterol, and when mice lack this protein (PDZD8-KO mice), they accumulate unhealthy levels of cholesteryl esters due to issues with lipophagy, which is how fats are broken down in the body.
  • The study found that PDZD8 is crucial for helping lipid droplets fuse with lysosomes for degradation, and a deficiency in this protein affects the mice's growth, behavior, and cognitive functions due to the lipid accumulation in the brain.

Article Abstract

Although dyslipidemia in the brain has been implicated in neurodegenerative disorders, the molecular mechanisms underlying its pathogenesis have been largely unclear. PDZD8 is a lipid transfer protein and mice deficient in PDZD8 (PDZD8-KO mice) manifest abnormal accumulation of cholesteryl esters (CEs) in the brain due to impaired lipophagy, the degradation system of lipid droplets. Here we show the detailed mechanism of PDZD8-dependent lipophagy. PDZD8 transports cholesterol to lipid droplets (LDs), and eventually promotes fusion of LDs and lysosomes. In addition, PDZD8-KO mice exhibit growth retardation, hyperactivity, reduced anxiety and fear, increased sensorimotor gating, and impaired cued fear conditioned memory and working memory. These results indicate that abnormal CE accumulation in the brain caused by PDZD8 deficiency affects emotion, cognition and adaptive behavior, and that PDZD8 plays an important role in the maintenance of brain function through lipid metabolism.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854033PMC
http://dx.doi.org/10.1186/s13041-023-01002-4DOI Listing

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