ArticleNature communications2024
Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells.Nature communications · 2026Article
- Structural-functional network decoupling in early stage amyotrophic lateral sclerosis reveals cell-type specific transcriptional signatures.BMC medicine · 2026Article
- Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.Stem cell reports · 2026Review
- Exploring retinal microglia: development, degeneration, and iPSC-derived model systems.Brain structure & function · 2026Review
- A high-throughput, quantitative platform using 2D dissociated human cerebral organoids to model neuroinflammation in Alzheimer's disease.NPJ dementia · 2026Article
- Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?Neurobiology of disease · 2026Review
- A Missense Mutation in Close Proximity of ALS-linked PFN1 Mutations Causes Only Early-onset Paget Disease of Bone.The Journal of clinical endocrinology and metabolism · 2025Article
- Tuberculous meningitis alters the proteomic landscape of brain-derived extracellular vesicles.bioRxiv : the preprint server for biology · 2025Article
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.Research square · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.bioRxiv : the preprint server for biology · 2025Article
- ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice.Nature communications · 2025Article
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- Identification of unique biomarkers for proliferative diabetic retinopathy with tractional retinal detachment by proteomics profiling of vitreous humor.Scientific reports · 2025Article
- Review
- Using ALS to understand profilin 1's diverse roles in cellular physiology.Cytoskeleton (Hoboken, N.J.) · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
Abstract
Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited evidence of lipid dysmetabolism, autophagy dysregulation and deficient phagocytosis, a canonical microglia function. Mutant PFN1 also displayed enhanced binding affinity for PI3P, a critical signaling molecule involved in autophagic and endocytic processing. Our cumulative data implicate a gain-of-toxic function for mutant PFN1 within the autophagic and endo-lysosomal pathways, as administration of rapamycin rescued phagocytic dysfunction in ALS-PFN1 iMGs. These outcomes demonstrate the utility of iMGs for neurodegenerative disease research and implicate microglial vesicular degradation pathways in the pathogenesis of these disorders.
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Registered trials
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.