Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease
Gurses Murat Serdar1,*, Ural Mustafa Numan1, Gulec Mehmet Akif2, Akyol Omer3, Akyol Sumeyya4
1Department of Forensic Medicine, School of Medicine, Uludag University, Bursa, Turkey 2Department of Medical Biochemistry, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey 3Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey 4Department of Medical Biology, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey
The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals. Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer’s disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.
Figure 1. Domain structure of ADAMTS proteins (It was adapted from Apte SS  and Stanton et al. )
Figure 2. The representation of the effects of ADAMTS on Tau production. Reelin binds to its receptors and activates phosphatidylinositol-3-kinase (PI3K) and protein kinase B (PKB/Akt). It leads a remarkable inhibition in glycogen synthase kinase 3β (GSK3β), which is an enzyme that regulates phosphorylation of the microtubule-stabilizing protein tau. After ADAMTS digest Reelin, depressed reelin level may in turn increase tau phosphorylation at the end of the signaling pathway. (It was adapted from the resources Krstic D , Hisanaga A , and Yu NN ).
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