ArticleBrain pathology (Zurich, Switzerland)2012
Kallikrein 6 regulates early CNS demyelination in a viral model of multiple sclerosis.
Article in Brain pathology (Zurich, Switzerland), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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
23 citing papers in PubMed, 41 citations in OpenAlex.
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis.Clinical proteomics · 2024Article
- Systemic Inflammation Leads to Changes in the Intracellular Localization of KLK6 in Oligodendrocytes in Spinal Cord White Matter.Neurochemical research · 2023Article
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- Involvement of Kallikrein-Related Peptidases in Nervous System Disorders.Frontiers in cellular neuroscience · 2020Article
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.Biological chemistry · 2018Article
- A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.The Journal of biological chemistry · 2018Article
- Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.Scientific reports · 2017Article
- Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis.Biological chemistry · 2016Article
- Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury.Neurobiology of disease · 2016Article
- Genetic targeting of protease activated receptor 2 reduces inflammatory astrogliosis and improves recovery of function after spinal cord injury.Neurobiology of disease · 2015Article
- Gray matter-related proteins are associated with childhood-onset multiple sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2015Article
- Unleashing the therapeutic potential of human kallikrein-related serine proteases.Nature reviews. Drug discovery · 2015Review
- Involvement of Kallikrein-Related Peptidases in Normal and Pathologic Processes.Disease markers · 2015Review
- Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response.Biological chemistry · 2014Article
- Metastasis of ovarian cancer is mediated by kallikrein related peptidases.Clinical & experimental metastasis · 2014Review
- Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration.Journal of neuropathology and experimental neurology · 2013Article
- Kallikrein 6 signals through PAR1 and PAR2 to promote neuron injury and exacerbate glutamate neurotoxicity.Journal of neurochemistry · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Kallikrein 6 (Klk6) is a secreted serine protease that is elevated in active multiple sclerosis lesions and patient sera. To further evaluate the involvement of Klk6 in chronic progressive demyelinating disease, we determined its expression in the brain and spinal cord of SJL mice infected with Theiler's murine encephalomyelitis virus (TMEV) and assessed the effects of Klk6-neutralizing antibodies on disease progression. Klk6 RNA expression was elevated in the brain and spinal cord by 7 days postinfection (dpi). Thereafter, Klk6 expression persisted primarily in the spinal cord reaching a peak of fivefold over controls at mid-chronic stages (60 dpi-120 dpi). Significant elevations in Klk6 RNA were also induced in splenocytes stimulated with viral capsid proteins in vitro and in activated human acute monocytic leukemia cells. Klk6-neutralizing antibodies reduced TMEV-driven brain and spinal cord pathology and delayed-type hypersensitivity (DTH) responses when examined at early chronic time points (40 dpi). Reductions in spinal cord pathology included a decrease in activated monocytes/microglia and reductions in the loss of myelin basic protein (MBP). By 180 dpi, pathology scores no longer differed between groups. These findings point to regulatory activities for Klk6 in the development and progression of central nervous system (CNS) inflammation and demyelination that can be effectively targeted through the early chronic stages with neutralizing antibody.
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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.