Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.
Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.
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DOI：
10.3390/ijms22031413
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发表时间：
2021-01-30
影响因子：
5.6
通讯作者：
Bungau S
中科院分区：
文献类型：
--
作者：
Behl T;Kaur G;Sehgal A;Bhardwaj S;Singh S;Buhas C;Judea-Pusta C;Uivarosan D;Munteanu MA;Bungau S
神经变性是指神经系统或神经元失去其结构、功能或两者，导致神经元进行性变性或死亡，以及组织系统明确的关联，从而导致临床表现的病理状态。在几种神经退行性疾病（ND）中，神经炎症已被证明先于神经退行性疾病。目前还没有药物可以延缓或治疗神经变性。虽然ND的病因和潜在原因仍不明确，但基质金属蛋白酶（MMPs）显然在ND的进展中起着至关重要的作用。基质金属蛋白酶（MMPs）是一种含锌（Zn 2+）的内肽酶蛋白家族，是中枢神经系统（CNS）中参与各种生物学和病理学过程的关键因子。目前的审查描绘了几个新出现的证据表明，在ND的进展中，MMPs的影响，其中它们调节几个过程，如（神经）炎症，小胶质细胞活化，淀粉样蛋白肽降解，血脑屏障（BBB）破坏，多巴胺能细胞凋亡和α-突触核蛋白调节，导致神经毒性和神经元死亡。通过PubMed、MEDLINE等检索迄今为止已发表的论文，同时使用我们手稿中突出显示的选择性关键词。我们还旨在阐明MMPs在CNS中的病理生理学作用，并将我们的注意力集中在其在ND中的有害和有益作用上，特别关注帕金森病（PD）、肌萎缩侧索硬化（ALS）、阿尔茨海默病（AD）、多发性硬化（MS）和亨廷顿病（HD），并讨论了针对MMPs的各种治疗策略，其可以作为ND的潜在调节剂。随着时间的推移，已经开发了几种药物，以克服挑战，并开辟了制造MMPs选择性调节剂的可能性，以破译NDs中MMPs的多方面功能。在临床上仍有更大的需要对其进行探索。
Neurodegeneration is the pathological condition, in which the nervous system or neuron loses its structure, function, or both, leading to progressive degeneration or the death of neurons, and well-defined associations of tissue system, resulting in clinical manifestations. Neuroinflammation has been shown to precede neurodegeneration in several neurodegenerative diseases (NDs). No drug is yet known to delay or treat neurodegeneration. Although the etiology and potential causes of NDs remain widely indefinable, matrix metalloproteinases (MMPs) evidently have a crucial role in the progression of NDs. MMPs, a protein family of zinc (Zn2+)-containing endopeptidases, are pivotal agents that are involved in various biological and pathological processes in the central nervous system (CNS). The current review delineates the several emerging evidence demonstrating the effects of MMPs in the progression of NDs, wherein they regulate several processes, such as (neuro)inflammation, microglial activation, amyloid peptide degradation, blood brain barrier (BBB) disruption, dopaminergic apoptosis, and α-synuclein modulation, leading to neurotoxicity and neuron death. Published papers to date were searched via PubMed, MEDLINE, etc., while using selective keywords highlighted in our manuscript. We also aim to shed a light on pathophysiological effect of MMPs in the CNS and focus our attention on its detrimental and beneficial effects in NDs, with a special focus on Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), multiple sclerosis (MS), and Huntington’s disease (HD), and discussed various therapeutic strategies targeting MMPs, which could serve as potential modulators in NDs. Over time, several agents have been developed in order to overcome challenges and open up the possibilities for making selective modulators of MMPs to decipher the multifaceted functions of MMPs in NDs. There is still a greater need to explore them in clinics.
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影响因子：
9
作者：
Barcia, C.;Ros, C. M.;Annese, V.;Gomez, A.;Ros-Bernal, F.;Aguado-Llera, D.;Martinez-Pagan, M. E.;de Pablos, V.;Fernandez-Villalba, E.;Herrero, M. T.
通讯作者：
Herrero, M. T.
影响因子：
5.3
作者：
Brkic, Marjana;Balusu, Sriram;Vandenbroucke, Roosmarijn E.
通讯作者：
Vandenbroucke, Roosmarijn E.
DOI：
10.1007/s00018-015-1992-1
发表时间：
2016-01
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Baranger K;Marchalant Y;Bonnet AE;Crouzin N;Carrete A;Paumier JM;Py NA;Bernard A;Bauer C;Charrat E;Moschke K;Seiki M;Vignes M;Lichtenthaler SF;Checler F;Khrestchatisky M;Rivera S
通讯作者：
Rivera S
影响因子：
1.7
作者：
Beuche, W;Yushchenko, M;Weber, F
通讯作者：
Weber, F
影响因子：
64.8
作者：
Bell, Robert D.;Winkler, Ethan A.;Singh, Itender;Sagare, Abhay P.;Deane, Rashid;Wu, Zhenhua;Holtzman, David M.;Betsholtz, Christer;Armulik, Annika;Sallstrom, Jan;Berk, Bradford C.;Zlokovic, Berislav V.
通讯作者：
Zlokovic, Berislav V.