ArticleNeurobiology of disease2019
Reduction of matrix metalloproteinase 9 (MMP-9) protects motor neurons from TDP-43-triggered death in rNLS8 mice.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications.Scientific reports · 2021Trial
- The role of the peripheral immune system in mediating axonal dysfunction in early-stage amyotrophic lateral sclerosis: An age- and sex-based analysis.Neural regeneration research · 2026Article
- Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.Stem cell reports · 2026Review
- AAV9 gene therapy optimization for SMARD1/CMT2S: safety and long-term efficacy comparison of two vectors in a SMARD1 preclinical model.Journal of biomedical science · 2026Article
- A Slower-Progressing TDP-43 rNLS8 Mouse Model for ALS: Implications for Preclinical and Mechanistic Studies.Neuromolecular medicine · 2025Article
- Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials.Brain sciences · 2025Review
- Role of lipocalin-2 in amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2025Review
- Article
- Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models.Brain : a journal of neurology · 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
- C9orf72-ALS human iPSC microglia are pro-inflammatory and toxic to co-cultured motor neurons via MMP9.Nature communications · 2023Article
- Blood-CNS barrier dysfunction in amyotrophic lateral sclerosis: Proposed mechanisms and clinical implications.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury.Frontiers in cellular neuroscience · 2023Article
- Neutrophils: a subgroup of neglected immune cells in ALS.Frontiers in immunology · 2023Review
- Slow motor neurons resist pathological TDP-43 and mediate motor recovery in the rNLS8 model of amyotrophic lateral sclerosis.Acta neuropathologica communications · 2022Article
- How Molecular Topology Can Help in Amyotrophic Lateral Sclerosis (ALS) Drug Development: A Revolutionary Paradigm for a Merciless Disease.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis.Frontiers in aging neuroscience · 2022Review
- A chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis.Clinical and translational medicine · 2022Review
- Microglial transcriptome analysis in the rNLS8 mouse model of TDP-43 proteinopathy reveals discrete expression profiles associated with neurodegenerative progression and recovery.Acta neuropathologica communications · 2021Article
- Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Therapeutic strategies are needed for the treatment of amyotrophic lateral sclerosis (ALS). One potential target is matrix metalloproteinase-9 (MMP-9), which is expressed only by fast motor neurons (MNs) that are selectively vulnerable to various ALS-relevant triggers. Previous studies have shown that reduction of MMP-9 function delayed motor dysfunction in a mouse model of familial ALS. However, given that the majority of ALS cases are sporadic, we propose preclinical testing in a mouse model which may be more clinically translatable: rNLS8 mice. In rNLS8 mice, neurodegeneration is triggered by the major pathological hallmark of ALS, TDP-43 mislocalization and aggregation. MMP-9 was targeted in 3 different ways in rNLS8 mice: by AAV9-mediated knockdown, using antisense oligonucleotide (ASO) technology, and by genetic modification. All 3 strategies preserved the motor unit during disease, as measured by MN counts, tibialis anterior (TA) muscle innervation, and physiological recordings from muscle. However, the strategies that reduced MMP-9 beyond the motor unit lead to premature deaths in a subset of rNLS8 mice. Therefore, selective targeting of MMP-9 in MNs could be beneficial in ALS, but side effects outside of the motor circuit may limit the most commonly used clinical targeting strategies.
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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.