The multifaceted role of metalloproteinases in physiological and pathological conditions in embryonic and adult brains. (August 2017)

• Record Type: Journal Article
• Authors: De Stefano, Maria Egle; Herrero, Maria Trinidad
• Is Part Of: Progress in neurobiology. Volume 155(2017:Aug.)
• Page Start: 36
• Page End: 56
• Publication Date: 2017-08
• Subjects: AD Alzheimer's disease -- ADAMs a disintegrin and metalloproteinase -- AJs adherens junctions -- AMPA α-amino-3-hydroxyl-5-methyl-4-isoxazole-proprionate -- APP amyloid precursor protein -- AQP4 aquaporin 4 -- Aβ amyloid-β peptides -- BBB blood brain barrier -- BDNF brain derived neurotrophic factor -- BM basement membrane -- CAMs cell adhesion molecules -- CNS central nervous system -- CSF cerebral spinal fluid -- DG dystroglycan -- EAE experimental autoimmune encephalomyelitis -- ECM extracellular matrix -- ET-1 endothelin-1 -- GJs gap junctions -- IGF insulin-like growth factor -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- LBs Lewy bodies -- LPS lipopolysaccharide -- LTP long term potentiation -- l-LTP late phase long term potentiation -- MBP myelin basic protein -- MMPs metalloproteinases -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- MS multiple sclerosis -- MT-MMPs membrane-type MMPs -- NGF nerve growth factor -- NMDA N-methyl-d-aspartate -- NVU neurovascular unit -- 6-OHDA 6-hydroxydopamine -- PARP poly (ADP-ribose) polymerase -- PNS peripheral nervous system -- PD Parkinson's disease -- PMB parenchymal basement membrane -- RNS reactive nitrogen species -- ROS reactive oxygen species -- SC superior colliculus -- SN substantia nigra -- SNAP-25 synaptosomal-associated protein 25 kDa -- TIMPs tissue inhibitors of metalloproteinases -- TJs tight junctions -- TNFα tumor necrosis factor-α -- ZO-1 zona occludens-1; Metalloproteinases -- Brain disorders -- Development -- Nervous system repair -- Neuroinflammation -- Neurodegenerative diseases; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2016.08.002
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: Matrix metalloproteinases play important roles in different physiological and pathological conditions of both developing and mature brain. We highlight and discuss MMP multifaceted potentialities, from beneficial to adverse, in different brain processes and conditions. We suggest cautious modulation of MMP activities when considering them as therapeutic targets in brain pathologies. We auspicate the need for more research in order to design optimal drugs that target specific MMPs. Abstract: Matrix metalloproteinases (MMPs) are a large family of ubiquitous extracellular endopeptidases, which play important roles in a variety of physiological and pathological conditions, from the embryonic stages throughout adult life. Their extraordinary physiological "success" is due to concomitant broad substrate specificities and strict regulation of their expression, activation and inhibition levels. In recent years, MMPs have gained increasing attention as significant effectors in various aspects of central nervous system (CNS) physiology. Most importantly, they have been recognized as main players in a variety of brain disorders having different etiologies and evolution. A common aspect of these pathologies is the development of acute or chronic neuroinflammation. MMPs play an integral part in determining the result of neuroinflammation, in some cases turning its beneficial outcome into a harmful one. This review summarizes the most relevant studies concerning the physiology of MMPs, highlighting their involvement in both the developing and mature CNS, in long-lasting and acute brain diseases and, finally, in nervous system repair. Recently, a concerted effort has been made in identifying therapeutic strategies for major brain diseases by targeting MMP activities. However, from this revision of the literature appears clear that MMPs have multifaceted functional characteristics, which modulate physiological processes in multiple ways and with multiple consequences. Therefore, when choosing MMPs as possible targets, great care must be taken to evaluate the delicate balance between their activation and inhibition and to determine at which stage of the disease and at what level they become active in order maximize chances of success.