@Article{biocell.2026.081123,
AUTHOR = {Mi Ri Kim, Ok-Hyeon Kim, Hyun Jung Lee},
TITLE = {Dysregulated Mechanotransduction in Brain Pathologies: How Physical Forces Contribute to Neurodegeneration},
JOURNAL = {BIOCELL},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/biocell/online/detail/27089},
ISSN = {1667-5746},
ABSTRACT = {Aging and brain injury remodel the central nervous system (CNS) physical microenvironment, yet the contribution of these mechanical changes to neurodegenerative disease remains underappreciated. While traditional models emphasize biochemical mechanisms, emerging evidence indicates that altered tissue stiffness, extracellular matrix composition, and interstitial fluid dynamics actively reprogram intracellular signaling via dysregulated mechanotransduction. This review describes key physical cues shaping the brain microenvironment, including substrate rigidity and fluid flow within the cerebrospinal fluid (CSF) and glymphatic system. We discuss how aging and injury-induced alterations disrupt mechanotransductive signaling compared to physiological conditions. Although candidate mechanosensors remain incompletely characterized, several are highlighted, including stretch-activated calcium channels like Piezo1 and Transient Receptor Potential Vanilloid 4 (TRPV4) and stiffness-responsive pathways involving focal adhesion kinase and Yes-associated protein 1 (YAP1)/Transcriptional co-activator with PDZ-binding motif (TAZ). We examine how these altered pathways influence the progression of neurodegenerative disorders and brain injury–associated pathologies. By integrating mechanobiology into neurodegenerative research, this review establishes physical forces as active disease drivers and identifies mechanotransduction as a promising frontier for the diagnosis and treatment of various brain pathologies.},
DOI = {10.32604/biocell.2026.081123}
}