Tags

Type your tag names separated by a space and hit enter

Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia.
Geroscience. 2019 10; 41(5):671-679.G

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.

Authors+Show Affiliations

Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA.Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA. Department of Neuroscience, University of Kentucky, Lexington, KY, 40536, USA. Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, 40536, USA.Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA. Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA.Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA. Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA.Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg., 800 S. Limestone Street, Lexington, KY, 40536, USA. linda.vaneldik@uky.edu. Department of Neuroscience, University of Kentucky, Lexington, KY, 40536, USA. linda.vaneldik@uky.edu. Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, 40536, USA. linda.vaneldik@uky.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31104189

Citation

Braun, David J., et al. "Genetic Knockout of Myosin Light Chain Kinase (MLCK210) Prevents Cerebral Microhemorrhages and Attenuates Neuroinflammation in a Mouse Model of Vascular Cognitive Impairment and Dementia." GeroScience, vol. 41, no. 5, 2019, pp. 671-679.
Braun DJ, Bachstetter AD, Sudduth TL, et al. Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia. Geroscience. 2019;41(5):671-679.
Braun, D. J., Bachstetter, A. D., Sudduth, T. L., Wilcock, D. M., Watterson, D. M., & Van Eldik, L. J. (2019). Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia. GeroScience, 41(5), 671-679. https://doi.org/10.1007/s11357-019-00072-4
Braun DJ, et al. Genetic Knockout of Myosin Light Chain Kinase (MLCK210) Prevents Cerebral Microhemorrhages and Attenuates Neuroinflammation in a Mouse Model of Vascular Cognitive Impairment and Dementia. Geroscience. 2019;41(5):671-679. PubMed PMID: 31104189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia. AU - Braun,David J, AU - Bachstetter,Adam D, AU - Sudduth,Tiffany L, AU - Wilcock,Donna M, AU - Watterson,D Martin, AU - Van Eldik,Linda J, Y1 - 2019/05/19/ PY - 2019/02/11/received PY - 2019/04/25/accepted PY - 2019/5/20/pubmed PY - 2020/5/22/medline PY - 2019/5/20/entrez KW - Cerebrovascular KW - Knockout KW - Microhemorrhage KW - Myosin light chain kinase KW - Neuroinflammation KW - Vascular cognitive impairment and dementia SP - 671 EP - 679 JF - GeroScience JO - Geroscience VL - 41 IS - 5 N2 - 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. SN - 2509-2723 UR - https://www.unboundmedicine.com/medline/citation/31104189/Genetic_knockout_of_myosin_light_chain_kinase__MLCK210__prevents_cerebral_microhemorrhages_and_attenuates_neuroinflammation_in_a_mouse_model_of_vascular_cognitive_impairment_and_dementia_ L2 - https://doi.org/10.1007/s11357-019-00072-4 DB - PRIME DP - Unbound Medicine ER -