MMPs: a novel drug target for schizophrenia

Schizophrenia, a multifactorial disorder, is associated with dopaminergic hyperactivity, dysregulated glutamatergic neurotransmission, neuroinflammation and extracellular matrix (ECM) disturbances. MMPs, a group of structurally related proteolytic enzymes, are responsible for remodeling of ECM that maintains synaptic functions and blood-brain barrier (BBB) patency. Overstimulation of MMPs by neuroinflammation triggers ECM abnormalities that directly or indirectly alter neuronal functions like synaptic plasticity and damage to BBB. MMP-mediated ECM abnormality plays a central role in the pathogenesis of schizophrenia.

The current review discusses the mechanistic involvement of MMPs in the pathogenesis of schizophrenia and briefly gives an overview on the recent studies on various MMP modulators.

Overexpression of MMPs and imbalance between MMP versus tissue inhibitors of metalloproteinase are associated with various ECM disturbances in the schizophrenic brain. Therefore, MMPs can be projected as potential therapeutic target for treatment and/or prevention of positive, negative and cognitive symptoms of schizophrenia. From past decade, scientific community is focusing on broad spectrum MMP modulators as potential therapeutic moieties for prevention of plethora of neurological, cardiovascular and pulmonary diseases. In future, specific MMP modulators should be tailored to regulate ECM integrity and explored for their pharmacotherapeutic potential in schizophrenia.