ArticleActa neuropathologica2016
Presymptomatic activation of the PDGF-CC pathway accelerates onset of ALS neurodegeneration.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Neuroimaging findings in preclinical amyotrophic lateral sclerosis models-How well do they mimic the clinical phenotype? A systematic review.Frontiers in veterinary science · 2023Pooled it
- Vascular profiling of the spinal cord and cortex reveals region-specific endothelial dysfunction and fibroblast remodeling in human ALS.Acta neuropathologica communications · 2026Article
- PDGFR-α Mediated the Neuroinflammation and Autophagy via the JAK2/STAT3 Signaling Pathway Contributing to Depression-Like Behaviors in Myofascial Pain Syndrome Rats.Molecular neurobiology · 2025Article
- Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis.Aging and disease · 2024Review
- Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation.JCI insight · 2024Article
- Diabetes and the treatment of ischemic stroke.Journal of diabetes and its complications · 2022Review
- Article
- Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.Seminars in thrombosis and hemostasis · 2022Review
- Breached Barriers: A Scoping Review of Blood-Central Nervous System Barrier Pathology in Amyotrophic Lateral Sclerosis.Frontiers in cellular neuroscience · 2022Article
- Proteomic Profiling of the Substantia Nigra to Identify Determinants of Lewy Body Pathology and Dopaminergic Neuronal Loss.Journal of proteome research · 2021Article
- Altered perivascular fibroblast activity precedes ALS disease onset.Nature medicine · 2021Article
- Blocking PDGF-CC signaling ameliorates multiple sclerosis-like neuroinflammation by inhibiting disruption of the blood-brain barrier.Scientific reports · 2020Article
- Emerging links between cerebrovascular and neurodegenerative diseases-a special role for pericytes.EMBO reports · 2019Review
- Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model.Disease models & mechanisms · 2019Article
- Impaired tissue barriers as potential therapeutic targets for Parkinson's disease and amyotrophic lateral sclerosis.Metabolic brain disease · 2018Review
- PDGF/PDGFR axis in the neural systems.Molecular aspects of medicine · 2018Review
- Article
- Article
- Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke.Acta neuropathologica · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown origins. Neurodegeneration in ALS mouse models occurs together with signs of disrupted blood-spinal cord barrier (BSCB) and regressed capillary network, but the molecular pathways contributing to these vascular pathologies remain unknown. We show that motor neurons of human sporadic ALS patients (n = 12) have increased gene expression of PDGFC and its activator PLAT and presymptomatic activation of the PDGF-CC pathway in SOD1 (G93A) mice leads to BSCB dysfunction. Decrease of Pdgfc expression in SOD1 (G93A) mice restored vascular barrier properties, reduced motor neuron loss and delayed symptom onset by up to 3 weeks. Similarly, lower expression levels of PDGFC or PLAT in motor neurons of sporadic ALS patients were correlated with older age at disease onset. PDGF-CC inhibition and restoration of BSCB integrity did not prevent capillary regression at disease end stage. Lower vessel density was found in spinal cords of sporadic ALS patients and the degree of regression in SOD1 (G93A) mice correlated with more aggressive progression after onset regardless of BSCB status. We conclude that PDGF-CC-induced BSCB dysfunction can contribute to timing of ALS onset, allow insight into disease origins and development of targeted novel therapies.
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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.