Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
Int J Mol Sci. 2023 Apr 18;24(8):7435. doi: 10.3390/ijms24087435.
The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect cellular functions and may result in disease. However, most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix in disease pathogenesis. Thus, due to the ECM's diversified biological roles, increasing interest in its involvement in disease, and the lack of sufficient compiled evidence regarding its relationship with Parkinson's disease (PD) pathology, we aimed to compile the existing evidence to boost the current knowledge on the area and provide refined guidance for the future research. Here, in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google Scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson's disease (PD). A literature search was conducted up until 10 February 2023. The overall hits from the database and manual search for proteomic and transcriptome studies were 1243 and 1041 articles, respectively. Following a full-text review, 10 articles from proteomic and 24 from transcriptomic studies were found to be eligible for inclusion. According to proteomic studies, proteins such as collagens, fibronectin, annexins, and tenascins were recognized to be differentially expressed in Parkinson's disease. Transcriptomic studies displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson's disease. A limited number of relevant studies were accessed from our search, indicating that much work remains to be carried out to better understand the roles of the ECM in neurodegeneration and Parkinson's disease. However, we believe that our review will elicit focused primary studies and thus support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson's disease.
大脑的细胞外基质（ECM）是一种由大量生物活性大分子组成的动态结构，这些大分子调节细胞事件。由于遗传变异或环境应激，这些大分子的结构、组织和功能发生变化，被认为会影响细胞功能，并可能导致疾病。然而，迄今为止，大多数机制研究通常侧重于疾病的细胞方面，而较少关注调节细胞外基质动态性质的过程与疾病发病机制的相关性。因此，由于 ECM 具有多样化的生物学作用，对其在疾病中的作用的兴趣日益增加，并且缺乏与帕金森病（PD）病理学相关的充分综合证据，我们旨在汇集现有证据，以提高该领域的现有知识水平，并为未来的研究提供更精细的指导。在这篇综述中，我们从 PubMed 和 Google Scholar 收集了死后脑组织和诱导多能干细胞（iPSC）相关研究，以确定、总结和描述帕金森病（PD）中大脑细胞外基质成分表达的常见大分子改变。文献检索截止到 2023 年 2 月 10 日。数据库和手动搜索蛋白质组学和转录组学研究的总命中数分别为 1243 篇和 1041 篇。经过全文审查，从蛋白质组学研究中发现了 10 篇符合条件的文章，从转录组学研究中发现了 24 篇符合条件的文章。根据蛋白质组学研究，发现胶原蛋白、纤维连接蛋白、膜联蛋白和 tenascin 等蛋白在帕金森病中表达差异。转录组学研究显示，帕金森病中存在失调的途径，包括细胞外基质-受体相互作用、焦点黏附和细胞黏附分子。从我们的搜索中获取了数量有限的相关研究，这表明为了更好地理解细胞外基质在神经退行性变和帕金森病中的作用，仍有大量工作要做。然而，我们相信我们的综述将引发重点的初步研究，并因此支持正在进行的发现和开发帕金森病诊断生物标志物和治疗剂的努力。
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