ArticleProceedings of the National Academy of Sciences of the United States of America2006
Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 145 citations in OpenAlex.
- Early disruptions in brain capillary blood flow control in a mouse model of Alzheimer's disease.The Journal of general physiology · 2026Article
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- The SHIP1-inflammatory-lipid axis in Alzheimer's disease: from genetic risk to spatiotemporal mechanistic insights.Journal of neuroinflammation · 2026Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Carvacrol improves neurological function by inhibiting TRPM7-mediated BBB disruption and hemorrhage after TBI.Acta neuropathologica communications · 2025Article
- Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer's Disease: Implications for Autophagy Dysfunction.International journal of molecular sciences · 2025Article
- The role of branched chain aminotransferase in the interrelated pathways of type 2 diabetes mellitus and Alzheimer's disease.Journal of diabetes and metabolic disorders · 2025Review
- TRPM7 contributes to pyroptosis and its involvement in status epilepticus.Journal of neuroinflammation · 2024Article
- Endocytosis and Alzheimer's disease.GeroScience · 2024Review
- Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities.FEBS open bio · 2024Review
- Lipophorin receptors genetically modulate neurodegeneration caused by reduction of Psn expression in the aging Drosophila brain.Genetics · 2024Article
- New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Alzheimer's disease induced neurons bearingFrontiers in cellular neuroscience · 2024Article
- Effect of truncation on TRPM7 channel activity.Channels (Austin, Tex.) · 2023Article
- Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer's disease.Molecular neurodegeneration · 2023Review
- α-Synuclein-dependent increases in PIP5K1γ drive inositol signaling to promote neurotoxicity.Cell reports · 2023Article
- Review
- Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene.International journal of molecular sciences · 2022Review
- Brain lipidomics: From functional landscape to clinical significance.Science advances · 2022Review
- TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target.Molecular neurodegeneration · 2022Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important cellular effector whose functions include the regulation of ion channels and membrane trafficking. Aberrant PIP2 metabolism has also been implicated in a variety of human disease states, e.g., cancer and diabetes. Here we report that familial Alzheimer's disease (FAD)-associated presenilin mutations cause an imbalance in PIP2 metabolism. We find that the transient receptor potential melastatin 7 (TRPM7)-associated Mg2+ -inhibited cation (MIC) channel underlies ion channel dysfunction in presenilin FAD mutant cells, and the observed channel deficits are restored by the addition of PIP2, a known regulator of the MIC/TRPM7 channel. Lipid analyses show that PIP2 turnover is selectively affected in FAD mutant presenilin cells. We also find that modulation of cellular PIP2 closely correlates with 42-residue amyloid beta-peptide (Abeta42) levels. Our data suggest that PIP2 imbalance may contribute to Alzheimer's disease pathogenesis by affecting multiple cellular pathways, such as the generation of toxic Abeta42 as well as the activity of the MIC/TRPM7 channel, which has been linked to other neurodegenerative conditions. Thus, our study suggests that brain-specific modulation of PIP2 may offer a therapeutic approach in Alzheimer's disease.
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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.