Proteins and transcriptional dysregulation of the brain extracellular matrix in Parkinson’s disease: A systematic review

Abstract

AbstractThe 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 the cellular functions, and may result in disease. 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 on disease pathogenesis. 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). 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. Limited number of relevant studies were accessed from our search indicating that much work still remains to be done 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.