ArticleMolecular brain2023
PDZD8-deficient mice manifest behavioral abnormalities related to emotion, cognition, and adaptation due to dyslipidemia in the brain.
Article in Molecular brain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- PDZD8 overexpression alleviates early brain injury via regulating MERCs integrity after experimental subarachnoid hemorrhage.Journal of neuroinflammation · 2026Article
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.Genes, brain, and behavior · 2026Article
- Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.bioRxiv : the preprint server for biology · 2026Article
- PDZD8 Dysregulation Mediates RVLM Neuronal Hyperexcitation Via Activation of CaMolecular neurobiology · 2025Article
- LYVAC/PDZD8 is a lysosomal vacuolator.Science (New York, N.Y.) · 2025Article
- Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice.Molecular autism · 2025Article
- Lysosomes' fallback strategies: more than just survival or death.Frontiers in cell and developmental biology · 2025Review
- Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders.Neural regeneration research · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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