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Cited by 389Fatty Acid Research and HealthLipid metabolism and biosynthesisLipid Membrane Structure and Behavior

Phosphatidylserine in the brain: Metabolism and function

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Kim, Hee-Yong, Huang, Bill X., Spector, Arthur A.·2014·Progress in Lipid Research
DOI 10.1016/j.plipres.2014.06.002PMC PMC4258547
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Abstract

Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear.

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  • Lipid classes PS, PE, sulfatide, cerebroside and PA are important to cognitive functions.

    “Brain lipidomics analysis indicates that apoE3-Jac expression increases several classes of lipids, such as PS, PE, sulfatide, cerebroside and PA, which are important to cognitive functions (38–40).”

    From <i>APOE3</i> -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [38]

    Section 9.1 (page unavailable) reports cognitive improvements after PS supplementation, supporting a link between PS and cognition. The paper discusses PE mainly as a substrate for PS synthesis; the passages found do not establish cognitive roles for PE, sulfatide, cerebroside, or PA. The apoE3-Jac lipidomics result is presented as the citing authors’ own finding, not as a claim attributed to this source. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Deficits of lipids have been implicated in the pathophysiology of Alzheimer's disease.

    “Brain is highly enriched in lipid contents; the deficits of lipids have been implicated in the pathophysiology of AD (37, 38).”

    From <i>APOE3</i> -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [38]

    Section 9 (Phosphatidylserine and cognitive function; page unavailable) reports reduced DHA content in phosphatidylserine in brain tissue from patients with Alzheimer’s disease. That supports a specific lipid change, but the authors say its contribution to pathogenesis is unknown and the proposed link remains open to question; the broader claim about lipid deficits in AD pathophysiology goes beyond the passage. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Kim, H.-Y., Huang, B. X., & Spector, A. A.
Affiliations
National Institutes of Health (US)
Corresponding author
Kim, Hee-Yong
ORCID
Kim, Hee-Yong
Venue
Progress in Lipid Research
Publisher
Elsevier BV
Published
2014-10
Volume
56
Pages
1-18
ISSN
0163-7827 (ISSN-L)
DOI
10.1016/j.plipres.2014.06.002
PMC
PMC4258547
OpenAlex
W2004447739
Cited by
389
References
3
Citations by year
2026: 44 · 2025: 46 · 2024: 54 · 2023: 52 · 2022: 39 · 2021: 45 · 2020: 29 · 2019: 26 · 2018: 24 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 1
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Progress in Lipid Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism (ZIAAA000284)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
phosphatidylserine, brain phospholipids, phosphatidylserine synthase, phosphatidylserine synthesis, docosahexaenoic acid, neuronal membrane, Akt signaling, protein kinase C signaling, neurotransmitter release, ethanol effects, memory
MeSH terms
Animals, Brain, Cell Differentiation, Cell Survival, Docosahexaenoic Acids, Humans, Models, Biological, Neurons, Phosphatidylserines, Biosynthetic Pathways

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