4.6 Review

Mechanotransduction: Exploring New Therapeutic Avenues in Central Nervous System Pathology

Journal

FRONTIERS IN NEUROSCIENCE
Volume 16, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2022.861613

Keywords

mechanobiology; extracellular matrix; mechanotransduction; central nervous system; neurodegenerative disorders

Categories

Funding

  1. FCT-Portuguese Foundation for Science and Technology-UT Austin Portugal Program [UTAPEXPL/NTec/0057/2017]
  2. Air Force Office of Scientific Research, United States [13074566]
  3. FCT-Portuguese Foundation for Science and Technology [SFRH/BD/140363/2018]
  4. Fundação para a Ciência e a Tecnologia [SFRH/BD/140363/2018] Funding Source: FCT

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This article explores the importance of mechanotransduction in the central nervous system (CNS) and its role in CNS pathology. It highlights the influence of the extracellular matrix's biochemical and biophysical components on cell behavior. Integrating mechanical properties into our understanding of CNS disease at a molecular level is crucial, as alterations in tissue mechanical properties are common in neurological diseases. Therefore, understanding CNS mechanotransduction pathways could lead to improvements in medical devices, diagnostic methods, and therapeutic strategies for CNS repair.
Cells are continuously exposed to physical forces and the central nervous system (CNS) is no exception. Cells dynamically adapt their behavior and remodel the surrounding environment in response to forces. The importance of mechanotransduction in the CNS is illustrated by exploring its role in CNS pathology development and progression. The crosstalk between the biochemical and biophysical components of the extracellular matrix (ECM) are here described, considering the recent explosion of literature demonstrating the powerful influence of biophysical stimuli like density, rigidity and geometry of the ECM on cell behavior. This review aims at integrating mechanical properties into our understanding of the molecular basis of CNS disease. The mechanisms that mediate mechanotransduction events, like integrin, Rho/ROCK and matrix metalloproteinases signaling pathways are revised. Analysis of CNS pathologies in this context has revealed that a wide range of neurological diseases share as hallmarks alterations of the tissue mechanical properties. Therefore, it is our belief that the understanding of CNS mechanotransduction pathways may lead to the development of improved medical devices and diagnostic methods as well as new therapeutic targets and strategies for CNS repair.

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