The DOI matches its Crossref record; 376 of the 376 references it cites were found in a registry or an index.
Phosphoinositides: Roles in the Development of Microglial-Mediated Neuroinflammation and Neurodegeneration
Open accessAbstract
Microglia are increasingly recognized as vital players in the pathology of a variety of neurodegenerative conditions including Alzheimer’s (AD) and Parkinson’s (PD) disease. While microglia have a protective role in the brain, their dysfunction can lead to neuroinflammation and contributes to disease progression. Also, a growing body of literature highlights the seven phosphoinositides, or PIPs, as key players in the regulation of microglial-mediated neuroinflammation. These small signaling lipids are phosphorylated derivates of phosphatidylinositol, are enriched in the brain, and have well-established roles in both homeostasis and disease.Disrupted PIP levels and signaling has been detected in a variety of dementias. Moreover, many known AD disease modifiers identified via genetic studies are expressed in microglia and are involved in phospholipid metabolism. One of these, the enzyme PLCγ2 that hydrolyzes the PIP species PI(4,5)P 2 , displays altered expression in AD and PD and is currently being investigated as a potential therapeutic target.Perhaps unsurprisingly, neurodegenerative conditions exhibiting PIP dyshomeostasis also tend to show alterations in aspects of microglial function regulated by these lipids. In particular, phosphoinositides regulate the activities of proteins and enzymes required for endocytosis, toll-like receptor signaling, purinergic signaling, chemotaxis, and migration, all of which are affected in a variety of neurodegenerative conditions. These functions are crucial to allow microglia to adequately survey the brain and respond appropriately to invading pathogens and other abnormalities, including misfolded proteins. AD and PD therapies are being developed to target many of the above pathways, and although not yet investigated, simultaneous PIP manipulation might enhance the beneficial effects observed. Currently, only limited therapeutics are available for dementia, and although these show some benefits for symptom severity and progression, they are far from curative. Given the importance of microglia and PIPs in dementia development, this review summarizes current research and asks whether we can exploit this information to design more targeted, or perhaps combined, dementia therapeutics. More work is needed to fully characterize the pathways discussed in this review, but given the strength of the current literature, insights in this area could be invaluable for the future of neurodegenerative disease research.
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“PI(3,4,5)P3 can be converted back to PI(4,5)P2 by the protein phosphatase and tensin homology (PTEN) or converted into PI(3,4)P2 by SHIP1, which negatively regulates PI3K/Akt signaling (Fig. 2) [89–92].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [90]
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“SHIP1 is a phosphatase involved in phosphoinositide signaling.”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [90]
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Terzioglu, G., & Young-Pearse, T. L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00674-9 · Cited by 91
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Phosphoinositide signalling in cell motility and adhesion
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Metadata
- Authors
- Ernest James Phillips, T., & Maguire, E.
- Affiliations
- Cardiff University (GB)
- Corresponding author
- Maguire, Emily
- ORCID
- Maguire, Emily
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2021-03-26
- Volume
- 15
- Pages
- 652593-652593
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC8032904
- OpenAlex
- W3140288526
- Cited by
- 33
- References
- 376
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 2 · 2021: 3
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Alzheimer's Society
- Cardiff University
- UK Dementia Research Institute
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- phosphoinositides, microglia, neuroinflammation, neurodegeneration, Alzheimer's disease, Parkinson's disease, PLCγ2, phosphatidylinositol 4,5-bisphosphate, phospholipid metabolism, endocytosis, Toll-like receptor signaling, purinergic signaling, chemotaxis, microglial migration, microglial dysfunction
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