Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia

David J. Braun, Adam D. Bachstetter, Tiffany L. Sudduth, Donna M. Wilcock, D. Martin Watterson, Linda J. Van Eldik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The blood-brain barrier (BBB) is critical in maintenance of brain homeostasis, and loss of its functional integrity is a key feature across a broad range of neurological insults. This includes both acute injuries such as traumatic brain injury and stroke, as well as more chronic pathologies associated with aging, such as vascular cognitive impairment and dementia (VCID). A specific form of myosin light chain kinase (MLCK210) is a major regulator of barrier integrity in general, including the BBB. Studies have demonstrated the potential of MLCK210 as a therapeutic target for peripheral disorders involving tissue barrier dysfunction, but less is known about its potential as a target for chronic neurologic disorders. We report here that genetic knockout (KO) of MLCK210 protects against cerebral microhemorrhages and neuroinflammation induced by chronic dietary hyperhomocysteinemia. Overall, the results are consistent with an accumulating body of evidence supporting MLCK210 as a potential therapeutic target for tissue barrier dysfunction and specifically implicate it in BBB dysfunction and neuroinflammation in a model of VCID.

Original languageEnglish (US)
Pages (from-to)671-679
Number of pages9
JournalGeroScience
Volume41
Issue number5
DOIs
StatePublished - Oct 1 2019

Keywords

  • Cerebrovascular
  • Knockout
  • Microhemorrhage
  • Myosin light chain kinase
  • Neuroinflammation
  • Vascular cognitive impairment and dementia

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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