Matrix metalloproteinase-9: A magic drug target in neuropsychiatry?

Neuropsychiatric conditions represent a major medical and societal challenge. The etiology of these conditions is very complex and combines genetic and environmental factors. The latter, for example, excessive maternal or early postnatal inflammation, as well as various forms of psychotrauma, often act as triggers leading to mental illness after a prolonged latent period (sometimes years). Matrix metalloproteinase-9 (MMP-9) is an extracellularly and extrasynaptic operating protease that is markedly activated in response to the aforementioned environmental insults. MMP-9 has also been shown to play a pivotal role in the plasticity of excitatory synapses, which, in its aberrant form, has repeatedly been implicated in the etiology of mental illness. In this conceptual review, we evaluate the experimental and clinical evidence supporting the claim that MMP-9 is uniquely positioned to be considered a drug target for ameliorating the adverse effects of environmental insults on the development of a variety of neuropsychiatric conditions, such as schizophrenia, bipolar disorder, major depression, autism spectrum disorders, addiction, and epilepsy. We also identify specific challenges and bottlenecks hampering the translation of knowledge on MMP-9 into new clinical treatments for the conditions above and suggest ways to overcome these barriers.image Matrix metalloproteinase-9 (MMP-9) is an extracellularly and extrasynaptic operating protease that has been shown to play a functional role in a variety of physiological and pathological phenomena, including development, learning and memory, synaptic plasticity, and inflammation, as well as autism spectrum and mood disorders, schizophrenia, addiction and epileptogenesis. MMP-9 is markedly activated in response to various environmental insults, such as excessive maternal or early postnatal inflammation, as well as various forms of psychotrauma. Therefore, it can be proposed that MMP-9 is uniquely positioned to be considered a drug target for ameliorating the adverse effects of environmental insults on the development of a variety of neuropsychiatric conditions.image