MMP-12, a Promising Therapeutic Target for Neurological Diseases.
The role of matrix metalloproteinase-12 (MMP-12) in the pathogenesis of several inflammatory diseases such as chronic obstructive pulmonary disease, emphysema, and asthma is well established. Several new studies and recent reports from our laboratory and others highlighted the detrimental role of MMP-12 in the pathogenesis of several neurological diseases. In this review, we discuss in detail the pathological role of MMP-12 and the possible underlying molecular mechanisms that contribute to disease pathogenesis in the context of central nervous system diseases such as stroke, spinal cord injury, and multiple sclerosis. The available information on the specific MMP-12 inhibitors used in several preclinical and clinical studies is also reviewed. Based on the reported studies to date, MMP-12 suppression could emerge as a promising therapeutic target for several CNS diseases that were discussed in this review.
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Dr., Peoria, IL, 61605, USA.
Bharath
B
Chelluboina
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Dr., Peoria, IL, 61605, USA.
Koteswara Rao
KR
Nalamolu
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Dr., Peoria, IL, 61605, USA.|Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.|Comprehensive Stroke Center, Illinois Neurological Institute, Peoria, IL, USA.
Jeffrey D
JD
Klopfenstein
Department of Pathology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
David M
DM
Pinson
Comprehensive Stroke Center, Illinois Neurological Institute, Peoria, IL, USA.|Department of Neurology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
David Z
DZ
Wang
Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Raghu
R
Vemuganti
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Dr., Peoria, IL, 61605, USA. krishnav@uic.edu.|Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL, USA. krishnav@uic.edu.|Department of Neurology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA. krishnav@uic.edu.
Krishna Kumar
KK
Veeravalli
D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism*
D053508:Matrix Metalloproteinase 12
Matrix metalloproteinase; Multiple sclerosis; Spinal cord injury; Stroke; Suppression