ArticleScientific reports2016
Selective Expression of Osteopontin in ALS-resistant Motor Neurons is a Critical Determinant of Late Phase Neurodegeneration Mediated by Matrix Metalloproteinase-9.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
- JP1 peptide modulates oxidative stress and autophagy via Keap1-Nrf2-ARE in ALS model mice.BMC medicine · 2026Article
- Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.Biomolecules · 2026Review
- Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice.Journal of neuroinflammation · 2026Article
- Axonal transport impairment as an upstream mechanism in amyotrophic lateral sclerosis pathogenesis.Frontiers in neuroscience · 2026Article
- Age-Related Changes in Matrix Metalloproteinase-9 Expression in Spinal Motor Neurons of Normal Mice.Cureus · 2025Article
- Optogenetic and Endogenous Modulation of CaInternational journal of molecular sciences · 2025Review
- ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice.Nature communications · 2025Article
- Thoracic Spinal Cord Contusion Impacts on Lumbar Enlargement: Molecular Insights.Molecular neurobiology · 2025Article
- Exercise, disease state and sex influence the beneficial effects of Fn14-depletion on survival and muscle pathology in the SOD1Skeletal muscle · 2024Article
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
- Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration.Cell reports · 2024Article
- Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration.Journal of neuroinflammation · 2024Article
- Selective vulnerability of motor neuron types and functional groups to degeneration in amyotrophic lateral sclerosis: review of the neurobiological mechanisms and functional correlates.Brain structure & function · 2024Review
- Associations of cortical SPP1 and ITGAX with cognition and common neuropathologies in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Chemogenetic inhibition of TrkB signalling reduces phrenic motor neuron survival and size.Molecular and cellular neurosciences · 2023Article
- Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).International immunology · 2023Review
- A cellular taxonomy of the adult human spinal cord.Neuron · 2023Article
- LAG-3 expression in microglia regulated by IFN-γ/STAT1 pathway and metalloproteases.Frontiers in cellular neuroscience · 2023Article
- RNA Sequencing and Spatial Transcriptomics in Traumatic Spinal Cord Injury (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Impaired disassembly of the axon initial segment restricts mitochondrial entry into damaged axons.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) MNs are more vulnerable than fast fatigue-resistant (FR) or slow (S) MNs. The reason for this selective vulnerability remains enigmatic. We report here that the extracellular matrix (ECM) protein osteopontin (OPN) is selectively expressed by FR and S MNs and ALS-resistant motor pools, whereas matrix metalloproteinase-9 (MMP-9) is selectively expressed by FF MNs. OPN is secreted and accumulated as extracellular granules in ECM in three ALS mouse models and a human ALS patient. In SOD1(G93A) mice, OPN/MMP-9 double positivity marks remodeled FR and S MNs destined to compensate for lost FF MNs before ultimately dying. Genetic ablation of OPN in SOD1(G93A) mice delayed disease onset but then accelerated disease progression. OPN induced MMP-9 up-regulation via αvβ3 integrin in ChAT-expressing Neuro2a cells, and also induced CD44-mediated astrocyte migration and microglial phagocytosis in a non-cell-autonomous manner. Our results demonstrate that OPN expressed by FR/S MNs is involved in the second-wave neurodegeneration by up-regulating MMP-9 through αvβ3 integrin in the mouse model of ALS. The differences in OPN/MMP-9 expression profiles in MN subsets partially explain the selective MN vulnerability in ALS.
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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.