Implication of matrix metalloproteinases in regulating neuronal disorder.
Neurological disorder is an abnormal condition of the nervous system that occurs due to the structural and biochemical abnormalities of nerves in brain and spinal cord. The nervous system, once exposed, has a limited capacity of self-repair. Neurodegeneration refers to the phenomenon of the structural and functional loss of neurons and the rate of which is accelerated by aging. Recent studies identified the blood brain barrier as hotspot of damage due to neurodegeneration. Depending on the location and severity of damage, the neurons succumb to death through the apoptotic, autophagic and necrotic pathways. The neurological system reorients the structure of neuronal circuits in order to maintain the neuronal plasticity during neurological disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis etc. Matrix metalloproteinases (MMPs), a family of Zn(2+) dependent endopeptidases play an important role in those neurodegenerative disorders. Recent studies implicated the role of MMPs in acute neuroinflammatory damage as well as in chronic neurodegeneration. The critical function of individual MMPs in tissue repair is also very important. MMPs serve important functions in the central nervous system (CNS) during growth and development. Besides, MMPs are important in neuronal damage in acute and chronic conditions as well as repair processes. Studies reveal that MMPs and the tissue inhibitors of metalloproteinases (TIMPs) play pivotal roles in pathogenesis and recovery of neurons. The expression and activities of MMPs are regulated by signaling molecules, TIMPs, cell surface receptors and transcription factors. In this review, we attempt to elucidate the role of MMPs in neurodegeneration and their functional mechanism in repairing the CNS. We also provide information for the therapeutics in neuronal disorder in the perspective of MMP regulation.
Drug Development Diagnostic and Biotechnology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Jadavpur, Kolkata, 700032, India, abhi_biochem81@yahoo.in.
Abhishek
A
Mukherjee
Snehasikta
S
Swarnakar
D000818:Animals; D016923:Cell Death; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology; D009422:Nervous System Diseases / Q000201:enzymology* / Q000473:pathology; D009473:Neuronal Plasticity; D000066829:Neuroprotection
D020782:Matrix Metalloproteinases