Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.

Lepeta, Katarzyna; Kaczmarek, Leszek

doi:10.1093/schbul/sbv036

Cited by 68 publications

(50 citation statements)

References 68 publications

(92 reference statements)

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“…). The possible role of MMP‐9 in the context of synaptic plasticity has been recently reviewed (Lepeta and Kaczmarek ). MMP‐9 also plays an important role in inflammatory responses that have been repeatedly implicated in schizophrenia (Leza et al .…”

Section: Pathologies: Predisposition Diagnosis and Therapy (Animal mentioning

confidence: 99%

MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

Vafadari

Salamian

Kaczmarek

2016

Journal of Neurochemistry

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301

257

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Matrix metalloproteinase-9 (MMP-9) is a member of the metzincin family of mostly extracellularly operating proteases. Despite the fact that all of these enzymes might be target promiscuous, with largely overlapping catalogs of potential substrates, MMP-9 has recently emerged as a major and apparently unique player in brain physiology and pathology. The specificity of MMP-9 may arise from its very local and time-restricted actions, even when released in the brain from cells of various types, including neurons, glia, and leukocytes. In fact, the quantity of MMP-9 is very low in the naive brain, but it is markedly activated at the levels of enzymatic activity, protein abundance, and gene expression following various physiological stimuli and pathological insults. Neuronal MMP-9 participates in synaptic plasticity by controlling the shape of dendritic spines and function of excitatory synapses, thus playing a pivotal role in learning, memory, and cortical plasticity. When improperly unleashed, MMP-9 contributes to a large variety of brain disorders, including epilepsy, schizophrenia, autism spectrum disorder, brain injury, stroke, neurodegeneration, pain, brain tumors, etc. The foremost mechanism of action of MMP-9 in brain disorders appears to be its involvement in immune/inflammation responses that are related to the enzyme's ability to process and activate various cytokines and chemokines, as well as its contribution to bloodbrain barrier disruption, facilitating the extravasation of leukocytes into brain parenchyma. However, another emerging possibility (i.e., the control of MMP-9 over synaptic plasticity) should not be neglected. The translational potential of MMP-9 has already been recognized in both the diagnosis and treatment domains. The most striking translational aspect may be the discovery of MMP-9 up-regulation in a mouse model of Fragile X syndrome, quickly followed by human studies and promising clinical trials that have sought to inhibit MMP-9. With regard to diagnosis, suggestions have been made to use MMP-9 alone or combined with tissue inhibitor of matrix metalloproteinase-1 or brain-derived neurotrophic factor as disease biomarkers.

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Section: Pathologies: Predisposition Diagnosis and Therapy (Animal mentioning

confidence: 99%

MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

Vafadari

Salamian

Kaczmarek

2016

Journal of Neurochemistry

Self Cite

301

257

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“…Substantial evidence has indeed suggested significant roles for MMPs, especially MMP‐9, in neurotransmitter receptor availability and synapse function (reviewed in Michaluk et al . ; Lepeta and Kaczmarek ; Vafadari et al . ).…”

Section: Synapse Structure and Functionmentioning

confidence: 99%

Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students

Lepeta

Lourenco

Schweitzer

et al. 2016

Journal of Neurochemistry

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279

220

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Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions. Thus, optimal synaptic communication is required for proper brain physiology, and slight perturbations of synapse function can lead to brain disorders. In fact, increasing evidence has demonstrated the relevance of synapse dysfunction as a major determinant of many neurological diseases. This notion has led to the concept of synaptopathies as brain diseases with synapse defects as shared pathogenic features. In this review, which was initiated at the 13th International Society for Neurochemistry Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental disorders (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer and Parkinson disease). We finally discuss the appropriateness and potential implications of gathering synapse diseases under a single term. Understanding common causes and intrinsic differences in diseaseassociated synaptic dysfunction could offer novel clues toward synapse-based therapeutic intervention for neurological and neuropsychiatric disorders.

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“…In vitro cell migration assays using mouse NSCs indicate that Wnt/β-catenin signaling also promotes cell migration via cross talk with prostaglandin E2 (PGE2) signaling. This pathway leads to transcriptional upregulation of Ctnnb1 , Ptgs2 , Ccnd1 , Mmp9 [137] - all of which, likely not coincidentally, have been linked to the etiopathology of ASD and Scz [138,139,140,141,142,143,144,145]. …”

Section: Neural Precursor Migrationmentioning

confidence: 99%

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

Mulligan

Cheyette

2016

Complex Psychiatry

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Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions. Simultaneously, large-scale human genomic studies are providing evidence that sequence variation in Wnt signal pathway genes contributes to pathogenesis in several psychiatric disorders. This article reviews neurodevelopmental and postneurodevelopmental functions of Wnt signaling, highlighting mechanisms, whereby its disruption might contribute to psychiatric illness, and then reviews the most reliable recent genetic evidence supporting that mutations in Wnt pathway genes contribute to psychiatric illness. We are proponents of the notion that studies in animal and hiPSC models informed by the human genetic data combined with the deep knowledge base and tool kits generated over the last several decades of basic neurodevelopmental research will yield near-term tangible advances in neuropsychiatry.

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Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.

Cited by 68 publications

References 68 publications

MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

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