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Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models

Cerebral cavernous malformation (CCM) is a cerebromicrovascular disease that affects up to 0.5% of the population. Vessel dilation, decreased endothelial cell–cell contact, and loss of junctional complexes lead to loss of brain endothelial barrier integrity and hemorrhagic lesion formation. Leakage...

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Autores principales: Phillips, Chelsea M., Stamatovic, Svetlana M., Keep, Richard F., Andjelkovic, Anuska V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105545/
https://www.ncbi.nlm.nih.gov/pubmed/35563390
http://dx.doi.org/10.3390/ijms23095000
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author Phillips, Chelsea M.
Stamatovic, Svetlana M.
Keep, Richard F.
Andjelkovic, Anuska V.
author_facet Phillips, Chelsea M.
Stamatovic, Svetlana M.
Keep, Richard F.
Andjelkovic, Anuska V.
author_sort Phillips, Chelsea M.
collection PubMed
description Cerebral cavernous malformation (CCM) is a cerebromicrovascular disease that affects up to 0.5% of the population. Vessel dilation, decreased endothelial cell–cell contact, and loss of junctional complexes lead to loss of brain endothelial barrier integrity and hemorrhagic lesion formation. Leakage of hemorrhagic lesions results in patient symptoms and complications, including seizures, epilepsy, focal headaches, and hemorrhagic stroke. CCMs are classified as sporadic (sCCM) or familial (fCCM), associated with loss-of-function mutations in KRIT1/CCM1, CCM2, and PDCD10/CCM3. Identifying the CCM proteins has thrust the field forward by (1) revealing cellular processes and signaling pathways underlying fCCM pathogenesis, and (2) facilitating the development of animal models to study CCM protein function. CCM animal models range from various murine models to zebrafish models, with each model providing unique insights into CCM lesion development and progression. Additionally, these animal models serve as preclinical models to study therapeutic options for CCM treatment. This review briefly summarizes CCM disease pathology and the molecular functions of the CCM proteins, followed by an in-depth discussion of animal models used to study CCM pathogenesis and developing therapeutics.
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spelling pubmed-91055452022-05-14 Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models Phillips, Chelsea M. Stamatovic, Svetlana M. Keep, Richard F. Andjelkovic, Anuska V. Int J Mol Sci Review Cerebral cavernous malformation (CCM) is a cerebromicrovascular disease that affects up to 0.5% of the population. Vessel dilation, decreased endothelial cell–cell contact, and loss of junctional complexes lead to loss of brain endothelial barrier integrity and hemorrhagic lesion formation. Leakage of hemorrhagic lesions results in patient symptoms and complications, including seizures, epilepsy, focal headaches, and hemorrhagic stroke. CCMs are classified as sporadic (sCCM) or familial (fCCM), associated with loss-of-function mutations in KRIT1/CCM1, CCM2, and PDCD10/CCM3. Identifying the CCM proteins has thrust the field forward by (1) revealing cellular processes and signaling pathways underlying fCCM pathogenesis, and (2) facilitating the development of animal models to study CCM protein function. CCM animal models range from various murine models to zebrafish models, with each model providing unique insights into CCM lesion development and progression. Additionally, these animal models serve as preclinical models to study therapeutic options for CCM treatment. This review briefly summarizes CCM disease pathology and the molecular functions of the CCM proteins, followed by an in-depth discussion of animal models used to study CCM pathogenesis and developing therapeutics. MDPI 2022-04-30 /pmc/articles/PMC9105545/ /pubmed/35563390 http://dx.doi.org/10.3390/ijms23095000 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Phillips, Chelsea M.
Stamatovic, Svetlana M.
Keep, Richard F.
Andjelkovic, Anuska V.
Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models
title Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models
title_full Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models
title_fullStr Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models
title_full_unstemmed Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models
title_short Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models
title_sort cerebral cavernous malformation pathogenesis: investigating lesion formation and progression with animal models
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105545/
https://www.ncbi.nlm.nih.gov/pubmed/35563390
http://dx.doi.org/10.3390/ijms23095000
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