Rho-associated kinase inhibitors in cerebral cavernous malformations: a preclinical systematic review.

Irem Uslu¹, Ecem Senturk², Zeynep E Celikkiran³, Bilge Kara⁴, Merve G Turkmenel⁵, Berkay Kilic⁶, Omar Alomari⁷, Doga D Demir Yangi⁸, Kivanc Yangi⁹

¹Faculty of Medicine, Pamukkale University, Denizli, Türkiye.

²Faculty of Medicine, Lobachevsky University, Nizhny Novgorod, Russian Federation.

³Faculty of Medicine, Biruni University, Istanbul, Türkiye.

⁴Manavgat State Hospital, Antalya, Türkiye.

⁵Faculty of Medicine, Atilim University, Ankara, Türkiye.

⁶Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Türkiye.

⁷Hamidiye International School of Medicine, University of Health Sciences, Istanbul, Türkiye.

⁸Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.

⁹The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. kivancyangi@gmail.com.

PubMed DOI

Abstract

Cerebral cavernous malformations (CCMs) are vascular abnormalities characterized by clusters of dilated capillaries. They are most associated with loss-of-function mutations in three genes (Ccm1, Ccm2, and Pdcd10/Ccm3). In capillary endothelial cells, mutations activate the Rho-associated coiled-coil-containing protein kinase (ROCK), leading to non-heme iron deposition and lesion formation, thereb…

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