Evidence map›Paper›PMID 38017562›Full record

ReviewMolecular neurodegeneration2023

Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer's disease.

Gizem Terzioglu, Tracy L Young-Pearse

Open access · goldAbstract readReview
In one paragraph

Review in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
12.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 76 citations in OpenAlex.

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  9. miR-146a-5p mitigates ethanol-induced neuroinflammation by targeting Btg2-dependent microglial activation.Malawi medical journal : the journal of Medical Association of Malawi · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Gizem TerziogluAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Boston, MA, 02115, USA.
Tracy L Young-PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Rd, Boston, MA, 02115, USA. tpearse@bwh.harvard.edu.ORCID 0000-0001-7846-1542
Brigham and Women's Hospital · US

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI TANZI, RUDOLPH EMILE · 1998 to 2023
$51.3M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Alzheimer variants: Propagation of shared functional changes across cellular networksU01AG072572 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DE JAGER, PHILIP L, ST GEORGE-HYSLOP, PETER HENRY · 2021 to 2025
$8.5M
Probing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7M
Cell and Molecular Consequences of Alzheimer's Disease Genetic Variants on BBB Integrity and FunctionRF1NS117446 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2020 to 2020
$3.6M
NIA NIH HHS P01 AG015379NIA NIH HHS R01 AG055909NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG072572NIH HHS R01AG055909NIH HHS RF1NS117446NIH HHS U01AG072572NINDS NIH HHS RF1 NS117446
6 · The paper itself

Abstract

Recent genetic studies on Alzheimer's disease (AD) have brought microglia under the spotlight, as loci associated with AD risk are enriched in genes expressed in microglia. Several of these genes have been recognized for their central roles in microglial functions. Increasing evidence suggests that SHIP1, the protein encoded by the AD-associated gene INPP5D, is an important regulator of microglial phagocytosis and immune response. A recent study from our group identified SHIP1 as a negative regulator of the NLRP3 inflammasome in human iPSC-derived microglial cells (iMGs). In addition, we found evidence for a connection between SHIP1 activity and inflammasome activation in the AD brain. The NLRP3 inflammasome is a multiprotein complex that induces the secretion of pro-inflammatory cytokines as part of innate immune responses against pathogens and endogenous damage signals. Previously published studies have suggested that the NLRP3 inflammasome is activated in AD and contributes to AD-related pathology. Here, we provide an overview of the current understanding of the microglial NLRP3 inflammasome in the context of AD-related inflammation. We then review the known intracellular functions of SHIP1, including its role in phosphoinositide signaling, interactions with microglial phagocytic receptors such as TREM2 and evidence for its intersection with NLRP3 inflammasome signaling. Through rigorous examination of the intricate connections between microglial signaling pathways across several experimental systems and postmortem analyses, the field will be better equipped to tailor newly emerging therapeutic strategies targeting microglia in neurodegenerative diseases.

Indexed as

Alzheimer DiseaseBrainHumansInflammasomesMicrogliaNLR Family, Pyrin Domain-Containing 3 ProteinPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesInflammasomesINPP5D protein, humanNLR Family, Pyrin Domain-Containing 3 ProteinPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesAlzheimer’s DiseaseInflammationINPP5DMicrogliaNLRP3 inflammasomePhosphoinositide signalingSHIP1

Identifiers

PMID38017562
PMCPMC10685641
OpenAlexW4389109479

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.