ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 124 citations in OpenAlex.
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Evidence for cPLA2 activation in Alzheimer's disease synaptic pathology.Acta neuropathologica communications · 2026Article
- Lysophosphatidylethanolamine (LysoPE) in health and disease: a narrative review of its pathophysiological mechanisms and translational potential as a biomarker.Frontiers in cell and developmental biology · 2026Review
- Short-term ketogenic diet induces systemic lipidomic remodeling associated with metabolic adaptation in humans.Frontiers in nutrition · 2026Article
- Deciphering the three-dimensional biomolecular distribution in the Alzheimer's disease brain: A multiomic approach integrating immunohistochemistry with MALDI MS imaging.Analytica chimica acta · 2025Article
- Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.Molecular neurodegeneration · 2025Review
- Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications.Research (Washington, D.C.) · 2025Review
- Helicobacter pylori outer membrane vesicles directly promote Aβ aggregation and enhance Aβ toxicity in APP/PS1 mice.Communications biology · 2024Article
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Rodent Models of Alzheimer's Disease: Past Misconceptions and Future Prospects.International journal of molecular sciences · 2024Review
- Large-Scale Population-Based Studies of Blood Metabolome and Brain Health.Current topics in behavioral neurosciences · 2024Review
- An Overview of Recent Advances in the Neuroprotective Potentials of Fisetin against Diverse Insults in Neurological Diseases and the Underlying Signaling Pathways.Biomedicines · 2023Review
- Review
- From the Bush to the Brain: Preclinical Stages of Ethnobotanical Anti-Inflammatory and Neuroprotective Drug Discovery-An Australian Example.International journal of molecular sciences · 2023Review
- The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles.International journal of molecular sciences · 2023Review
- BACE1 and SCD1 are associated with neurodegeneration.Frontiers in aging neuroscience · 2023Article
- Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell-type lipidomics.Annals of the New York Academy of Sciences · 2022Review
- Animal models of Alzheimer's disease: Applications, evaluation, and perspectives.Zoological research · 2022Review
- Calcium-dependent cytosolic phospholipase AMolecular neurodegeneration · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The deregulation of cyclin-dependent kinase 5 (Cdk5) by p25 has been shown to contribute to the pathogenesis in a number of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). In particular, p25/Cdk5 has been shown to produce hyperphosphorylated tau, neurofibrillary tangles as well as aberrant amyloid precursor protein processing found in AD. Neuroinflammation has been observed alongside the pathogenic process in these neurodegenerative diseases, however the precise mechanism behind the induction of neuroinflammation and the significance in the AD pathogenesis has not been fully elucidated. In this report, we uncover a novel pathway for p25-induced neuroinflammation where p25 expression induces an early trigger of neuroinflammation in vivo in mice. Lipidomic mass spectrometry, in vitro coculture and conditioned media transfer experiments show that the soluble lipid mediator lysophosphatidylcholine (LPC) is released by p25 overexpressing neurons to initiate astrogliosis, neuroinflammation and subsequent neurodegeneration. Reverse transcriptase PCR and gene silencing experiments show that cytosolic phospholipase 2 (cPLA2) is the key enzyme mediating the p25-induced LPC production and cPLA2 upregulation is critical in triggering the p25-mediated inflammatory and neurodegenerative process. Together, our findings delineate a potential therapeutic target for the reduction of neuroinflammation in neurodegenerative diseases including AD.
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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.