ArticleNeurotoxicity research2015
Failure of Neuroprotection Despite Microglial Suppression by Delayed-Start Myeloperoxidase Inhibition in a Model of Advanced Multiple System Atrophy: Clinical Implications.
Article in Neurotoxicity research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 44 citations in OpenAlex.
- Multiple system atrophy: cure and care.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Multiple system atrophy: an update and emerging directions of biomarkers and clinical trials.Journal of neurology · 2024Review
- Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024Review
- Multi-Oxidant Environment as a Suicidal Inhibitor of Myeloperoxidase.Antioxidants (Basel, Switzerland) · 2023Article
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.Signal transduction and targeted therapy · 2023Review
- A Mouse Model of Multiple System Atrophy: Bench to Bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Inflammation in multiple system atrophy.Frontiers in immunology · 2023Review
- Thiocyanate Reduces Motor Impairment in the hMPO-A53T PD Mouse Model While Reducing MPO-Oxidation of Alpha Synuclein in Enlarged LYVE1/AQP4 Positive Periventricular Glymphatic Vessels.Antioxidants (Basel, Switzerland) · 2022Article
- Myeloperoxidase: Regulation of Neutrophil Function and Target for Therapy.Antioxidants (Basel, Switzerland) · 2022Review
- Microglia in Parkinson's Disease.Journal of Parkinson's disease · 2022Review
- Disease-Modifying Therapies for Multiple System Atrophy: Where Are We in 2022?Journal of Parkinson's disease · 2022Review
- Current experimental disease-modifying therapeutics for multiple system atrophy.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- The Add-On Effect ofFrontiers in nutrition · 2021Article
- Human myeloperoxidase (hMPO) is expressed in neurons in the substantia nigra in Parkinson's disease and in the hMPO-α-synuclein-A53T mouse model, correlating with increased nitration and aggregation of α-synuclein and exacerbation of motor impairment.Free radical biology & medicine · 2019Article
- Immunohistochemical and Molecular Investigations Show Alteration in the Inflammatory Profile of Multiple System Atrophy Brain.Journal of neuropathology and experimental neurology · 2018Article
- DNA damage and neurodegenerative phenotypes in aged Ciz1 null mice.Neurobiology of aging · 2018Article
- Myeloperoxidase-immunoreactive cells are significantly increased in brain areas affected by neurodegeneration in Parkinson's and Alzheimer's disease.Cell and tissue research · 2017Article
- Multiple System Atrophy - State of the Art.Current neurology and neuroscience reports · 2017Review
- Polymer brain-nanotherapeutics for multipronged inhibition of microglial α-synuclein aggregation, activation, and neurotoxicity.Biomaterials · 2016Article
- Therapeutic approaches in Parkinson's disease and related disorders.Journal of neurochemistry · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease. Post-mortem hallmarks of MSA neuropathology include oligodendroglial α-synuclein (αSYN) inclusions, striatonigral degeneration, olivopontocerebellar atrophy, and increased microglial activation that accompanies the wide spread neurodegeneration. Recently, we demonstrated upregulation of myeloperoxidase (MPO) in activated microglia and provided evidence for the role of microglial MPO in the mediation of MSA-like neurodegeneration (Stefanova et al. Neurotox Res 21:393-404, 2015). The aim of the current study was to assess the therapeutic potency of MPO inhibition (MPOi) in a model of advanced MSA. We replicated the advanced pathology of MSA by intoxicating transgenic PLP-α-synuclein transgenic mice with 3-nitropropionic acid (3NP). After onset of the full-blown pathology, MSA mice received either MPOi or vehicle over 3 weeks. Motor phenotype and neuropathology were analyzed to assess the therapeutic efficacy of MPOi compared to vehicle treatment in MSA mice. MPOi therapy initiated after the onset of severe MSA-like neuropathology in mice failed to attenuate motor impairments and neuronal loss within the striatum, substantia nigra pars compacta, inferior olives, pontine nuclei, and cerebellar cortex. However, we observed a significant reduction of microglial activation in degenerating brain areas. Further, nitrated αSYN accumulation was reduced in the striatonigral region. In summary, delayed-start MPOi treatment reduced microglial activation and levels of nitrated αSYN in a mouse model of advanced MSA. These effects failed to impact on motor impairments and neuronal loss in contrast to previously reported disease modifying efficacy of early-start therapy with MPOi in MSA.
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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.