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Cited by 129Sphingolipid Metabolism and SignalingLysosomal Storage Disorders ResearchNeurological diseases and metabolism

Role of Sphingolipid Metabolism in Neurodegeneration

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Alaamery, Manal, Albesher, Nour, Aljawini, Nora, Alsuwailm, Moneera, Massadeh, Salam, Wheeler, Michael A., Chao, Chun‐Cheih, Quintana, Francisco J.·2021·Journal of Neurochemistry
DOI 10.1111/jnc.15044PMC PMC7665988
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Abstract

Sphingolipids are a class of lipids highly enriched in the central nervous system (CNS), which shows great diversity and complexity, and has been implicated in CNS development and function. Alterations in sphingolipid metabolism have been described in multiple diseases, including those affecting the central nervous system (CNS). In this review, we discuss the role of sphingolipid metabolism in neurodegeneration, evaluating its direct roles in neuron development and health, and also in the induction of neurotoxic activities in CNS‐resident astrocytes and microglia in the context of neurologic diseases such as multiple sclerosis and Alzheimer's disease. Finally, we focus on the metabolism of gangliosides and sphingosine‐1‐phosphate, its contribution to the pathogenesis of neurologic diseases, and its potential as a candidate target for the therapeutic modulation of neurodegeneration. image

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  • Lysosomes are required for turnover of damaged, misfolded and aggregated proteins as part of proteostasis.

    “As part of the normal process of protein homeostasis (i.e., proteostasis), lysosomes are required for turnover of damaged, misfolded and aggregated proteins.2”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [2]

    The Introduction section on sphingosine-1-phosphate in neurodegeneration says autophagy helps prevent the accumulation of misfolded proteins in neurons. It does not state that lysosomes are required for this turnover or specifically address damaged and aggregated proteins in that context (no page number is available in our copy). (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Alaamery, M., Albesher, N., Aljawini, N., Alsuwailm, M., Massadeh, S., Wheeler, M. A., Chao, C., & Quintana, F. J.
Affiliations
  • King Abdulaziz City for Science and Technology (SA)
  • Brigham and Women's Hospital (US)
  • Broad Institute (US)
Corresponding author
Quintana, Francisco J.
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2020-07-03
Volume
158
Issue
1
Pages
25-35
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.15044
PMC
PMC7665988
OpenAlex
W3024990779
Cited by
129
References
4
Citations by year
2026: 18 · 2025: 29 · 2024: 26 · 2023: 22 · 2022: 21 · 2021: 10 · 2020: 3
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Multiple Sclerosis Society
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
sphingolipid metabolism, neurodegeneration, gangliosides, sphingosine-1-phosphate, astrocytes, microglia, neuroinflammation, multiple sclerosis, Alzheimer's disease, neuronal development, therapeutic target
MeSH terms
Animals, Central Nervous System Diseases, Gangliosides, Humans, Lysophospholipids, Sphingolipids, Sphingosine, Neurodegenerative Diseases, Lipid Metabolism

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