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@ARTICLE{Sandhoff:182155,
author = {R. Sandhoff$^*$ and K. Sandhoff},
title = {{N}euronal {G}anglioside and {G}lycosphingolipid ({GSL})
{M}etabolism and {D}isease : {C}ascades of {S}econdary
{M}etabolic {E}rrors {C}an {G}enerate {C}omplex
{P}athologies (in {LSD}s).},
journal = {Advances in neurobiology},
volume = {29},
issn = {2190-5215},
address = {New York, NY},
publisher = {Springer},
reportid = {DKFZ-2022-02466},
isbn = {978-3-031-12389-4 (print)},
pages = {333-390},
year = {2023},
note = {#EA:A411# / Adv Neurobiol = 2190-5223},
abstract = {Glycosphingolipids (GSLs) are a diverse group of membrane
components occurring mainly on the surfaces of mammalian
cells. They and their metabolites have a role in
intercellular communication, serving as versatile
biochemical signals (Kaltner et al, Biochem J
476(18):2623-2655, 2019) and in many cellular pathways.
Anionic GSLs, the sialic acid containing gangliosides (GGs),
are essential constituents of neuronal cell surfaces,
whereas anionic sulfatides are key components of myelin and
myelin forming oligodendrocytes. The stepwise biosynthetic
pathways of GSLs occur at and lead along the membranes of
organellar surfaces of the secretory pathway. After
formation of the hydrophobic ceramide membrane anchor of
GSLs at the ER, membrane-spanning glycosyltransferases (GTs)
of the Golgi and Trans-Golgi network generate cell
type-specific GSL patterns for cellular surfaces. GSLs of
the cellular plasma membrane can reach intra-lysosomal, i.e.
luminal, vesicles (ILVs) by endocytic pathways for
degradation. Soluble glycoproteins, the glycosidases, lipid
binding and transfer proteins and acid ceramidase are needed
for the lysosomal catabolism of GSLs at ILV-membrane
surfaces. Inherited mutations triggering a functional loss
of glycosylated lysosomal hydrolases and lipid binding
proteins involved in GSL degradation cause a primary
lysosomal accumulation of their non-degradable GSL
substrates in lysosomal storage diseases (LSDs). Lipid
binding proteins, the SAPs, and the various lipids of the
ILV-membranes regulate GSL catabolism, but also primary
storage compounds such as sphingomyelin (SM), cholesterol
(Chol.), or chondroitin sulfate can effectively inhibit
catabolic lysosomal pathways of GSLs. This causes cascades
of metabolic errors, accumulating secondary lysosomal GSL-
and GG- storage that can trigger a complex pathology
(Breiden and Sandhoff, Int J Mol Sci 21(7):2566, 2020).},
subtyp = {Review Article},
keywords = {Alzheimer (Other) / Catabolism (Other) / Degradation
(Other) / Development (Other) / Endosomal pathway (Other) /
Frontal lobe dementia (Other) / Ganglio-series (Other) /
Ganglioside (Other) / Genetic disease (Other) / Glycolipid
(Other) / Glycosphingolipid (Other) / Glycosyltransferase
(Other) / Hydrolase (Other) / Intra-lysosomal luminal
vesicle (ILV) (Other) / Lysosomal storage disease (LSD)
(Other) / Lysosome (Other) / Membrane-surface (Other) /
Metabolism (Other) / Neurodegenerative disease (Other) /
Neuron (Other) / Organelle (Other) / Parkinson (Other) /
Receptor (Other) / Secondary storage (Other) / Secretory
pathway (Other) / Sphingolipid-binding protein (SAP) (Other)
/ Sphingolipid-transfer protein (Other) / Topology (Other)},
cin = {A411},
ddc = {570},
cid = {I:(DE-He78)A411-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)16},
pubmed = {pmid:36255681},
doi = {DOI: 10.1007/978-3-031-12390-0_12},
url = {https://inrepo02.dkfz.de/record/182155},
}