基质金属蛋白酶
促炎细胞因子
神经科学
神经化学
阿尔茨海默病
金属蛋白酶
神经炎症
平衡
神经退行性变
痴呆
细胞外基质
内生
化学
疾病
生物
细胞生物学
医学
炎症
病理
内分泌学
免疫学
生物化学
作者
Hongyue Wang,Long Huang,Lei Wu,Jiaqi Lan,Feng Xu,Pingping Li,Ying Peng
出处
期刊:Cns & Neurological Disorders-drug Targets
[Bentham Science]
日期:2020-11-20
卷期号:19 (6): 402-416
被引量:14
标识
DOI:10.2174/1871527319666200812223007
摘要
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.
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