Watch a 42-minute research lecture from the Inaugural Brain Resilience Symposium exploring lysosome function and its critical role in brain health and disease. Delve into groundbreaking research on subcellular metabolism and organelle dysfunction, with particular focus on Batten disease and CLN3 deficiency. Learn about the accumulation of Glycerophosphodiesters in lysosomes, the essential role of choline in brain homeostasis, and discover a novel lysosomal phospholipid salvage pathway. Examine findings from endolysosomal CRISPR-Cas9 screening that identifies crucial lysosomal proteins, and understand the implications of SPNS1 deficiency on lysophospholipid transport. Presented by Monther Abu-Remaileh, this talk provides deep insights into the optimization of subcellular biochemistry and its potential impact on treating various human diseases.
Lysosome Function in Brain Health and Disease - From Tool Development to Novel Biology
Wu Tsai Neurosciences Institute, Stanford via YouTube
Overview
Syllabus
Intro
The lysosome is an example of the optimized subcellular biochemistry: it degrades macromolecules to recycle their nutrient content
Understanding these functions might be key for understanding a wide range of human disease
Subcellular metabolism as a new approach to study organelle dysfunction in human disease
Untargeted metabolomics reveals the accumulation of Glycerophosphodiesters (GPDs) in CLN3 deficient lysosomes
How does CLN3 deficiency lead to neuronal cell death in Batten disease?
Decreased contribution of GPC-derived choline to lipid biosynthesis in CLN3 KO-neurons
Lysosomal choline metabolism is essential for brain homeostasis
Choline: an essential metabolite in physiology
What are the principal sources of choline?
Endolysosomal CRISPR-Cas9 screen to identify lysosomal proteins important for surviving choline deprivation
Phosphocholine and choline are not accumulating in SPNS1- deficient lysosomes
SPNS1-deficient lysosomes accumulate lysophosphocholine (LPC) and lysophosphoethanolamine (LPE)
LPCs generated in lysosomes are trapped in SPNS1-deficient lysosomes
SPNS1 is a lysosomal lysophospholipid transporter
A novel lysosomal phospholipid salvage pathway
Taught by
Wu Tsai Neurosciences Institute, Stanford
