Does the functional polymorphism-1562C/T of MMP-9 gene influence brain disorders?

Abstract

Metalloproteinase-9 (MMP-9) is one of the most strongly expressed matrix metalloproteinases (MMPs) in the brain. The MMP-9 activity in the brain is strictly regulated, and any disruptions in this regulation contribute to a development of many disorders of the nervous system including multiple sclerosis, brain strokes, neurodegenerative disorders, brain tumors, schizophrenia, or Guillain-Barré syndrome. This article discusses a relationship between development of the nervous system diseases and the functional single nucleotide polymorphism (SNP) at position -1562C/T within the MMP-9 gene. A pathogenic influence of MMP-9-1562C/T SNP was observed both in neurological and psychiatric disorders. The presence of the allele T often increases the activity of the MMP-9 gene promoter and consequently the expression of MMP-9 when compared to the allele C. This leads to a change in the likelihood of an occurrence of diseases and modifies the course of certain brain diseases in humans, as discussed below. The presented data indicates that the MMP-9-1562C/T functional polymorphism influences the course of many neuropsychiatric disorders in humans suggesting a significant pathological role of the MMP-9 metalloproteinase in pathologies of the human central nervous system.

Selective vulnerability of motor neuron types and functional groups to degeneration in amyotrophic lateral sclerosis: review of the neurobiological mechanisms and functional correlates

“…This Zn 2+ -activated protease is functionally related to various cell surface proteins, including integrins, TrkA and TrkB receptors, and plays essential roles in neurodevelopment and synaptic plasticity (Verslegers et al 2013 ; Vafadari et al 2016 ) and regulation of axonal myelination and pruning (Reinhard et al 2015 ). MMP9 polymorphisms are among the principal risk factors for sporadic ALS (Zawislak et al 2009 ; Pabian-Jewula and Rylski 2023 ), with results of postmortem studies of ALS patients showing MMP9 levels ~ 2.5-fold lower in the oculomotor nucleus as compared to lumbar MNs (Brockington et al 2013 ). Accordingly, Kaplan and co-workers reported higher expression of MMP9 in ALS-vulnerable MNs of the SOD1 mouse model, with its overexpression in wild-type MNs sufficient to trigger axonal dieback (Kaplan et al 2014 ).…”

Identification of Molecular Mechanisms Responsible for the MMP-9-1562C/T Dependent Differential Regulation of Matrix Metalloproteinase-9 Expression in Human Neuron-like Cells

“…The data indicated that the MMP-9 polymorphism, even if it is not the leading player responsible for the development of many diseases, certainly does matter [14]. Until now, no one has demonstrated that MMP-9 expression is regulated by the MMP-9-1562C/T polymorphism in brain cells.…”