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Article type: Review Article
Authors: Kaminari, Archontiaa | Tsilibary, Effie C.b | Tzinia, Athinaa; *
Affiliations: [a] Institute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, Agia Paraskevi, Athens, Greece | [b] Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA
Correspondence: [*] Correspondence to: Dr. Athina Tzinia, Senior Researcher, Laboratory of Cell matrix pathobiology and extracellular space, Institute of Biosciences and Applications, National Center of Scientific Research “Demokritos”, Patr. Gregoriou E & 27 Neapoleos Str, Agia Paraskevi, Athens 15310, Greece. Tel.: + 30 210 650 3678; Fax: + 30 210 651 1767; E-mail: [email protected].
Abstract: Matrix metalloprotease 9 (MMP-9) is a 92 kDa type IV collagenase and a member of the family of endopeptidases. MMP-9 is involved in the degradation of extracellular matrix components, tissue remodeling, cellular receptor stripping, and processing of various signaling molecules. In the CNS, the effects of MMP-9 are quite complex, since it exerts beneficial effects including neurogenesis, angiogenesis, myelogenesis, axonal growth, and inhibition of apoptosis, or destructive effects including apoptosis, blood-brain barrier disorder, and demyelination. Likewise, in the periphery, physiological events, as the involvement of MMP-9 in angiogenesis, for instance in wound healing, can be turned into pathological, such as in tumor metastasis, depending on the state of the organism. Alzheimer’s disease is a neurodegenerative disorder, characterized by amyloid accumulation and deposition in the brain. Amyloidogenesis, however, also occurs in diseases of the periphery, such as type II diabetes mellitus, where an analogous type of amyloid, is deposited in the pancreas. Interestingly, both diseases exhibit similar pathology and disease progression, with insulin resistance being a major common denominator. Hence, combinatorial strategies searching new or existing molecules to apply for therapeutic use for both diseases are gaining momentum. MMP-9 is extensively studied due to its association with a variety of physiological and pathological processes. Consequently, meticulous design could render MMP-9 into a potential therapeutic target for Alzheimer’s disease and type 2 diabetes mellitus; two seemingly unrelated diseases.
Keywords: Alzheimer’s disease, amyloidogenesis, insulin resistance, MMP-9, type 2 diabetes mellitus
DOI: 10.3233/JAD-180035
Journal: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 1-16, 2018
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