Matrix metalloproteinase-3 in brain physiology and neurodegeneration

Abstract

Structural and functional synapse reorganization is one of the key issues of learning and memory mechanisms. Specific proteases, called matrix metalloproteinases (MMPs), play a pivotal role during learning-related modification of neural circuits. Different types of MMPs modify the extracellular perisynaptic environment, leading to the plastic changes in the synapses. In recent years, there has been an increasing interest in the role played by matrix metalloproteinase-3 (MMP-3) in various processes occurring in the mammalian brain, both in physiological and pathological conditions. In this review, we discuss a crucial function of MMP-3 in synaptic plasticity, learning, neuronal development, as well as in neuroregeneration. We discuss the involvement of MMP-3 in synaptic long-term potentiation, which is likely to have a profound impact on experiencedependent learning. On the other hand, we also provide examples of deleterious actions of uncontrolled MMP-3 activity on the central nervous system (CNS) and its contribution to Alzheimer's and Parkinson's diseases (AD and PD). Since the molecular mechanisms controlled by MMP-3 have a profound and diverse impact on physiological and pathological brain functioning, their deep understanding may be crucial for the development of more specific methods for the treatment of neuropsychiatric diseases.

Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives

“…It was examined that CSF samples from PPMS and RRMS patients showed an upsurge in the level of MMP-9 during both phases of MS. Although, MMP-9 was augmented in about 1 2 of the samples in PPMS patients with smaller amounts than in the remitting-relapsing period. They debated that this pinpoints the fact that macrophages and T-cells are mainly responsible for MMP-9 secretion in MS.…”

“…Recently, MT5-MMP has been identified as a key player in AD whose colocalization was found to be with amyloid plaques in the brain of AD patients, suggesting it as a participant of the remodeling of injured regions. Moreover, independent efforts from different teams have presented that MT5-MMP mediated APP processing results in the production of fragments via the activity of η-secretase, ultimately resulting in neurotoxic effects in vivo and in vitro [1,142].…”

Ocular TGF-β, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus

“…To date, only limited information is available regarding MMP-3 in the retina in health and disease. The fact that it cleaves several ECM and BM components and is involved in the activation of other MMPs, namely, MMP-9 [ 25 , 26 ], suggests a potential upstream regulatory role in DR. Interestingly, a pathological role of MMPs in several neurological diseases has been associated with its capability to degrade tight junction proteins and to compromise the blood-brain barrier [ 27 , 28 ].…”

Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients

“…In addition, it is involved in the proteolysis of various adhesion molecules like E-cadherin and L-selectin, growth factors like heparin-binding EGF-like growth factor, cytokines like TNF and IL-1 β , and proforms of other MMPs like proMMP-1, proMMP-3, and proMMP-9. In the brain, MMP-3 is essential for neurite outgrowth, neuronal plasticity, and remyelination [ 16 , 17 ].…”