The MMP-2/TIMP-2 System in Alzheimer Disease

Author(s): Hongyue Wang, Longjian Huang, Lei Wu, Jiaqi Lan, Xinhong Feng, Pingping Li*, Ying Peng*

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 19 , Issue 6 , 2020

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Graphical Abstract:


Alzheimer Disease (AD) is the most prevalent type of dementia. Pathological changes in the AD brain include Amyloid β-protein (Aβ) plaques and Neurofibrillary Tangles (NFTs), as well as extensive neuronal and synaptic loss. Matrix Metalloproteinase-2 (MMP-2) is a neutral, zinc-dependent protease that primarily targets extracellular matrix proteins. MMP-2 activity is strictly controlled, and its dysregulation has been implicated in a variety of pathologies, including AD. In this brief review, we discussed the contributions of dysregulated MMP-2 activity and an imbalanced interaction between MMP-2 and its endogenous inhibitor, Tissue Inhibitors of Metalloproteinase-2 (TIMP-2), to AD. We also described the underlying mechanisms of the effects of MMP-2/TIMP-2, both beneficial and detrimental, on AD, including: (1) MMP-2 directly degrades Aβ resulting in the clearance of Aβ deposits. Conversely, Aβ-induced MMP-2 may contribute to brain parenchymal destruction. (2) MMP-2 induces breakdown of BBB, and this deleterious effect could be reversed by TIMP-2. (3) MMP-2 disrupts oxidative homeostasis in AD. (4) MMP-2 has both proinflammatory/pro-angiogenetic and antiinflammatory/ anti-angiogenetic effects on AD. Besides, we discuss the clinical utility of MMP- 2/TIMP-2 as therapeutic targets for AD.

Keywords: Matrix metalloproteinase-2, tissue inhibitor of metalloproteinases-2, Alzheimer disease, blood-brain barrier, neuroinflammation, oxidative stress.

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Article Details

Year: 2020
Published on: 20 November, 2020
Page: [402 - 416]
Pages: 15
DOI: 10.2174/1871527319666200812223007
Price: $65

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