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基质金属蛋白酶在中枢神经系统中的生物学意义及病理生理作用

Biological significance and pathophysiological role of Matrix Metalloproteinases in the Central Nervous System.

作者信息

Ganguly Krishnendu, Adhikary Krishnendu, Acharjee Arup, Acharjee Papia, Trigun Surendra Kumar, Mutlaq Alaa Saeed, Ashique Sumel, Yasmin Sabina, Alshahrani Asma M, Ansari Mohammad Yousuf

机构信息

Department of Medical Lab Technology, Paramedical College Durgapur, Helen Keller Sarani, Durgapur 713212, West Bengal, India.

Molecular Omics Laboratory, Department of Zoology, University of Allahabad, Allahabad, Uttar Pradesh, India.

出版信息

Int J Biol Macromol. 2024 Sep 24;280(Pt 3):135967. doi: 10.1016/j.ijbiomac.2024.135967.

Abstract

Matrix Metalloproteinases (MMPs), which are endopeptidase reliant on zinc, are low in embryonic tissues but increases in response to a variety of physiological stimulus and pathological stresses. Neuro-glial cells, endothelial cells, fibroblasts, and leucocytes secrete MMPs, which cleave extracellular matrix proteins in a time-dependent manner. MMPs affect synaptic plasticity and the development of short-term memory by controlling the size, shape, and excitatory synapses' function through the lateral diffusion of receptors. In addition, MMPs influence the Extracellular Matrix proteins in the Peri-Neuronal Net at the Neuro-glial interface, which aids in the establishment of long-term memory. Through modulating neuronal, and glial cells migration, differentiation, Neurogenesis, and survival, MMPs impact brain development in mammals. In adult brains, MMPs play a beneficial role in physiological plasticity, which includes learning, memory consolidation, social interaction, and complex behaviors, by proteolytically altering a wide variety of factors, including growth factors, cytokines, receptors, DNA repair enzymes, and matrix proteins. Additionally, stress, depression, addiction, hepatic encephalopathy, and stroke may all have negative effects on MMPs. In addition to their role in glioblastoma development, MMPs influence neurological diseases such as epilepsy, schizophrenia, autism spectrum disorder, brain damage, pain, neurodegeneration, and Alzheimer's and Parkinson's. To help shed light on the potential of MMPs as a therapeutic target for neurodegenerative diseases, this review summarizes their regulation, mode of action, and participation in brain physiological plasticity and pathological damage. Finally, by employing different MMP-based nanotools and inhibitors, MMPs may also be utilized to map the anatomical and functional connectome of the brain, analyze its secretome, and treat neurodegenerative illnesses.

摘要

基质金属蛋白酶(MMPs)是一类依赖锌的内肽酶,在胚胎组织中含量较低,但会随着各种生理刺激和病理应激而增加。神经胶质细胞、内皮细胞、成纤维细胞和白细胞会分泌MMPs,它们会以时间依赖性方式裂解细胞外基质蛋白。MMPs通过控制受体的横向扩散来调节突触的大小、形状和兴奋性突触的功能,从而影响突触可塑性和短期记忆的形成。此外,MMPs还会影响神经胶质界面处神经元周围网络中的细胞外基质蛋白,这有助于长期记忆的建立。通过调节神经元和神经胶质细胞的迁移、分化、神经发生和存活,MMPs影响哺乳动物的大脑发育。在成人大脑中,MMPs通过蛋白水解作用改变多种因子,包括生长因子、细胞因子、受体、DNA修复酶和基质蛋白,从而在生理可塑性中发挥有益作用,包括学习、记忆巩固、社交互动和复杂行为。此外,应激、抑郁、成瘾、肝性脑病和中风都可能对MMPs产生负面影响。除了在胶质母细胞瘤发展中的作用外,MMPs还会影响癫痫、精神分裂症、自闭症谱系障碍、脑损伤、疼痛、神经退行性变以及阿尔茨海默病和帕金森病等神经系统疾病。为了有助于阐明MMPs作为神经退行性疾病治疗靶点的潜力,本综述总结了它们的调节、作用方式以及在大脑生理可塑性和病理损伤中的参与情况。最后,通过使用不同的基于MMP的纳米工具和抑制剂,MMPs还可用于绘制大脑的解剖和功能连接组、分析其分泌组以及治疗神经退行性疾病。

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