MMPs and ADAMs in neurological infectious diseases and multiple sclerosis.

Muri, Lukas Kilian; Leppert, David; Grandgirard, Denis; Leib, Stephen (2019). MMPs and ADAMs in neurological infectious diseases and multiple sclerosis. Cellular and molecular life sciences : CMLS, 76(16), pp. 3097-3116. Springer 10.1007/s00018-019-03174-6

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Metalloproteinases-such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs)-are involved in various diseases of the nervous system but also contribute to nervous system development, synaptic plasticity and neuroregeneration upon injury. MMPs and ADAMs proteolytically cleave many substrates including extracellular matrix components but also signaling molecules and receptors. During neuroinfectious disease with associated neuroinflammation, MMPs and ADAMs regulate blood-brain barrier breakdown, bacterial invasion, neutrophil infiltration and cytokine signaling. Specific and broad-spectrum inhibitors for MMPs and ADAMs have experimentally been shown to decrease neuroinflammation and brain damage in diseases with excessive neuroinflammation as a common denominator, such as pneumococcal meningitis and multiple sclerosis, thereby improving the disease outcome. Timing of metalloproteinase inhibition appears to be critical to effectively target the cascade of pathophysiological processes leading to brain damage without inhibiting the neuroregenerative effects of metalloproteinases. As the critical role of metalloproteinases in neuronal repair mechanisms and regeneration was only lately recognized, the original idea of chronic MMP inhibition needs to be conceptually revised. Recently accumulated research urges for a second chance of metalloproteinase inhibitors, which-when correctly applied and dosed-harbor the potential to improve the outcome of different neuroinflammatory diseases.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Muri, Lukas Kilian; Grandgirard, Denis and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1420-9071

Publisher:

Springer

Funders:

[4] Swiss National Science Foundation

Projects:

[UNSPECIFIED] Swiss National Science Foundation Grant 310030-162583

Language:

English

Submitter:

Stephen Leib

Date Deposited:

18 Sep 2019 17:34

Last Modified:

22 Oct 2019 21:12

Publisher DOI:

10.1007/s00018-019-03174-6

PubMed ID:

31172218

Uncontrolled Keywords:

Bacterial meningitis MMP Metalloproteinase Multiple sclerosis Neuroinfection Neuroinflammation

BORIS DOI:

10.7892/boris.133324

URI:

https://boris.unibe.ch/id/eprint/133324

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