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Cited by 96Neuropeptides and Animal PhysiologyNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

Glio‐ and neuro‐protection by prosaposin is mediated by orphan G‐protein coupled receptors GPR37L1 and GPR37

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Liu, Beihui, Mosienko, Valentina, Vaccari Cardoso, Barbara, Prokudina, Daria, Huentelman, Mathew, Teschemacher, Anja G., Kasparov, Sergey·2018·Glia
DOI 10.1002/glia.23480PMC PMC6492175
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Abstract

Discovery of neuroprotective pathways is one of the major priorities for neuroscience. Astrocytes are natural neuroprotectors and it is likely that brain resilience can be enhanced by mobilizing their protective potential. Among G-protein coupled receptors expressed by astrocytes, two highly related receptors, GPR37L1 and GPR37, are of particular interest. Previous studies suggested that these receptors are activated by a peptide Saposin C and its neuroactive fragments (prosaptide TX14(A)), which were demonstrated to be neuroprotective in various animal models by several groups. However, pairing of Saposin C or prosaptides with GPR37L1/GPR37 has been challenged and presently GPR37L1/GPR37 have regained their orphan status. Here, we demonstrate that in their natural habitat, astrocytes, these receptors mediate a range of effects of TX14(A), including protection from oxidative stress. The Saposin C/GPR37L1/GPR37 pathway is also involved in the neuroprotective effect of astrocytes on neurons subjected to oxidative stress. The action of TX14(A) is at least partially mediated by Gi-proteins and the cAMP-PKA axis. On the other hand, when recombinant GPR37L1 or GPR37 are expressed in HEK293 cells, they are not functional and do not respond to TX14(A), which explains unsuccessful attempts to confirm the ligand-receptor pairing. Therefore, this study identifies GPR37L1/GPR37 as the receptors for TX14(A), and, by extension of Saposin C, and paves the way for the development of neuroprotective therapeutics acting via these receptors.

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  • In astrocytes, PSAP promotes motility and neuroprotective function, and is upregulated in the brains of patients with AD.

    “In astrocytes, it promotes motility and neuroprotective function, and is upregulated in the brains of patients with AD. 47 , 48”

    From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [47]

    The Results section on astrocyte motility reports that PSAP depletion slowed movement in a scratch assay, while the Results section on oxidative stress links PSAP signaling in astrocytes to protection of co-cultured neurons. The paper does not report PSAP upregulation in the brains of patients with AD; its reported increase was in culture media after neurons were stressed. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Cited by

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Authors
Liu, B., Mosienko, V., Vaccari Cardoso, B., Prokudina, D., Huentelman, M., Teschemacher, A. G., & Kasparov, S.
Affiliations
  • University of Bristol (GB)
  • Department of Physiology, Pharmacology, and Neuroscience University of Bristol Bristol United Kingdom
  • Immanuel Kant Baltic Federal University (RU)
  • Translational Genomics Research Institute (US)
Corresponding author
  • Teschemacher, Anja G.
  • Kasparov, Sergey
ORCID
Venue
Glia
Publisher
Wiley
Published
2018-09-27
Volume
66
Issue
11
Pages
2414-2426
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
DOI
10.1002/glia.23480
PMC
PMC6492175
OpenAlex
W2894074987
Cited by
96
References
2
Citations by year
2026: 9 · 2025: 11 · 2024: 17 · 2023: 17 · 2022: 8 · 2021: 14 · 2020: 10 · 2019: 4 · 2018: 5
FWCI
3.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Glia (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Research Exeter (University of Exeter) (acceptedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/L019396/1)
  • Medical Research Council (MR/L020661/1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
prosaposin, saposin C, GPR37L1, GPR37, orphan G protein-coupled receptor, astrocytes, neuroprotection, oxidative stress, Gi protein, cAMP/PKA signaling
MeSH terms
Cyclic AMP, Adjuvants, Immunologic, Animals, Animals, Newborn, Astrocytes, Cell Movement, Cells, Cultured, Cerebral Cortex, Embryo, Mammalian, Colforsin, Humans, L-Lactate Dehydrogenase, Nerve Growth Factors, Neurons, Water, Wounds and Injuries, Rats, Wistar, Neuroprotective Agents, RNA Interference, Receptors, G-Protein-Coupled, Saposins, Rats, HEK293 Cells

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