ArticleJournal of neurochemistry2013
Critical role of calpain in spinal cord degeneration in Parkinson's disease.
Article in Journal of neurochemistry, 2013. 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.
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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, 39 citations in OpenAlex.
- Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases.Neurochemical research · 2022Pooled it
- Article
- Calpain-2 Regulates Kinesin and Dynein Dysfunction in Neurotoxin-Induced Motoneuron Injury.Brain sciences · 2026Article
- Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.Journal of cellular and molecular medicine · 2024Review
- Atractylenolide-I Ameliorates Motor Deficits and Reduces Inflammation of the Spinal Cord by SIRT1/PGC-1α Pathway in MPTP Subacute Mouse Model of Parkinson's Disease.Neuropsychiatric disease and treatment · 2024Article
- Article
- Molecular Mechanisms and Pathophysiological Significance of Eryptosis.International journal of molecular sciences · 2023Review
- Inhibition of Calpain Attenuates Degeneration of Substantia Nigra Neurons in the Rotenone Rat Model of Parkinson's Disease.International journal of molecular sciences · 2022Article
- Calpain activation and progression of inflammatory cycles in Parkinson's disease.Frontiers in bioscience (Landmark edition) · 2022Review
- Calpain mediated expansion of CD4+ cytotoxic T cells in rodent models of Parkinson's disease.Experimental neurology · 2020Article
- Dysregulation of BDNF/TrkB signaling mediated by NMDAR/CaJournal of neuroinflammation · 2020Article
- Therapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson's Disease.Frontiers in neuroscience · 2019Article
- Regulatory Effects of Neuroinflammatory Responses Through Brain-Derived Neurotrophic Factor Signaling in Microglial Cells.Molecular neurobiology · 2018Article
- Advantages of Structure-Based Drug Design Approaches in Neurological Disorders.Current neuropharmacology · 2017Review
- Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease.Acta pharmacologica Sinica · 2017Article
- Calpain inhibition as a possible new therapeutic target in multiple sclerosis.AIMS molecular science · 2017Article
- Critical role of calpain in inflammation.Biomedical reports · 2016Article
- Cobalt Protoporphyrin Upregulates Cyclooxygenase-2 Expression Through a Heme Oxygenase-Independent Mechanism.Molecular neurobiology · 2016Article
- Administration of low dose estrogen attenuates gliosis and protects neurons in acute spinal cord injury in rats.Journal of neurochemistry · 2016Article
- Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors.Acta pharmaceutica Sinica. B · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
While multiple molecular mechanisms contribute to midbrain nigrostriatal dopaminergic degeneration in Parkinson's disease (PD), the mechanism of damage in non-dopaminergic sites within the central nervous system, including the spinal cord, is not well-understood. Thus, to understand the comprehensive pathophysiology underlying this devastating disease, postmortem spinal cord tissue samples (cervical, thoracic, and lumbar segments) from patients with PD were analyzed compared to age-matched normal subjects or Alzheimer's disease for selective molecular markers of neurodegeneration and inflammation. Distal axonal degeneration, relative abundance of both sensory and motor neuron death, selective loss of ChAT(+) motoneurons, reactive astrogliosis, microgliosis, increased cycloxygenase-2 (Cox-2) expression, and infiltration of T cells were observed in spinal cord of PD patients compared to normal subjects. Biochemical analyses of spinal cord tissues revealed associated inflammatory and proteolytic events (elevated levels of Cox-2, expression and activity of μ- and m-calpain, degradation of axonal neurofilament protein, and concomitantly low levels of endogenous inhibitor - calpastatin) in spinal cord of PD patients. Thus, pathologically upregulated calpain activity in spinal cords of patients with PD may contribute to inflammatory response-mediated neuronal death, leading to motor dysfunction. We proposed calpain over-activation and calpain-calpastatin dysregulation driving in a cascade of inflammatory responses (microglial activation and T cell infiltration) and degenerative pathways culminating in axonal degeneration and neuronal death in spinal cord of Parkinson's disease patients. This may be one of the crucial mechanisms in the degenerative process.
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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.