Review
Biochemistry & Molecular Biology
Chelsea M. Phillips, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: Cerebral cavernous malformation is a cerebromicrovascular disease with significant impact on the population, leading to severe symptoms and complications. Understanding the function of CCM proteins is crucial for unraveling the disease pathogenesis and developing treatment strategies. Animal models play a key role in studying CCM pathogenesis and therapeutic development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Giulia Riolo, Claudia Ricci, Stefania Battistini
Summary: Cerebral cavernous malformations (CCMs) are vascular lesions primarily affecting microvasculature in the brain and spinal cord, with known genetic mutations causing protein dysfunction in endothelial cell adherens junctions. The three genes associated with CCM lead to loss of function, compromising vascular barrier integrity. This dysfunction can result in molecular disorganization and compromise cellular signaling within endothelial cells.
Article
Genetics & Heredity
Elzbieta Szczygiel-Pilut, Daniel Pilut, Michal Korostynski, Piotr Kopinski, Daniel P. Potaczek, Ewa Wypasek
Summary: This article describes a case of CCM in a Polish female with a single-nucleotide variant in the PDCD10 gene, which is the first genetically characterized case of FCCM in Poland.
Article
Biochemistry & Molecular Biology
Claudia Ricci, Alfonso Cerase, Giulia Riolo, Giuditta Manasse, Stefania Battistini
Summary: Cerebral cavernous malformations (CCMs) can cause symptoms such as headaches and seizures, with mutations in the KRIT1 gene accounting for a majority of familial cases and resulting in premature stop codons. Phenotypic variability and incomplete penetrance of symptoms in mutation carriers were observed among CCM patients.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Pablo Iruzubieta, David Campo-Caballero, Jon Equiza, Ines Albajar, Naroa Sulibarria, Raquel Saez, Naiara Andres, Elisabet Mondragon, Miren Zulaica, Ana de Arce, Miguel Urtasun, Adolfo Lopez de Munain
Summary: Familial CCM is an autosomal dominant inherited disorder related to mutations in KRIT1, Malcavernin or PDCD10, with clinical phenotype ranging from asymptomatic individuals to severe intracranial hemorrhage. Patients with PDCD10 mutations often exhibit a more aggressive course and frequently show multiple meningiomas. This study provides evidence for the pathogenicity of new mutations in CCM genes and supports previous findings on familial CCM and multiple meningiomas.
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Andrea Perrelli, Annalisa Bozza, Chiara Ferraris, Sara Osella, Andrea Moglia, Silvia Mioletti, Luigi Battaglia, Saverio Francesco Retta
Summary: This study investigated the therapeutic effects of multidrug-loaded lipid nanoemulsions in rescuing the pathological phenotype of CCM disease. The results showed that drug-loaded lipid nanoemulsions can rescue antioxidant responses, reactivate autophagy, and reduce the effect of pro-angiogenic factors better than the free drugs. This highlights the importance of developing a combinatorial preventive and therapeutic approach for CCM.
Article
Clinical Neurology
Alejandro N. Santos, Laurel Rauschenbach, Hannah Hadice Gull, Thiemo Florin Dinger, Mehdi Chihi, Yan Li, Stephan Tippelt, Christian Dohna-Schwake, Boerge Schmidt, Ramazan Jabbarli, Karsten H. Wrede, Ulrich Sure, Philipp Dammann
Summary: This study aimed to assess the functional outcome and predictors of single and multiple intracerebral hemorrhage (ICH) in pediatric patients with cerebral cavernous malformations (CCMs), and to evaluate the risk of a third bleed after the second ICH. The findings showed that brainstem cavernous malformation (BSCM) was associated with worse outcome after the second ICH. Functional outcome improved over time after an ICH, but worsened with each subsequent ICH compared to baseline or previous ICH. The second bleed was associated with neurological deterioration compared to the initial ICH, and this deterioration further worsened after a third ICH.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Philipp Dammann, Annika Herten, Alejandro N. Santos, Laurel Rauschenbach, Bixia Chen, Marvin Darkwah Oppong, Boerge Schmidt, Michael Forsting, Christoph Kleinschnitz, Ulrich Sure
Summary: This study assessed outcomes after surgery for brainstem cavernous malformations (BSCMs) and found that patients' health-related quality of life (HRQOL) was impaired post-surgery, especially in those with unfavorable functional outcomes. Psychological impairment was more significant in unfavorable outcome patients, while minimal in those with favorable outcomes. Symptoms related to brainstem and cranial nerves had a notable impact on HRQOL.
JOURNAL OF NEUROSURGERY
(2021)
Article
Biochemistry & Molecular Biology
Valerio Benedetti, Rosalia Canzoneri, Andrea Perrelli, Carlo Arduino, Andrea Zonta, Alfredo Brusco, Saverio Francesco Retta
Summary: Cerebral Cavernous Malformation (CCM) is a genetic cerebrovascular disease that can cause seizures, neurological deficits, and fatal intracerebral hemorrhage. It is associated with loss-of-function mutations in three genes and may have additional genetic modifiers. A study in Italy identified pathogenic variants in CCM genes in 29% of CCM cases, as well as variants in other genes related to oxidative stress and inflammation.
Article
Clinical Neurology
Romuald Girard, Yan Li, Agnieszka Stadnik, Robert Shenkar, Nicholas Hobson, Sharbel Romanos, Abhinav Srinath, Thomas Moore, Rhonda Lightle, Abdallah Shkoukani, Amy Akers, Timothy Carroll, Gregory A. Christoforidis, James Koenig, Cornelia Lee, Kristina Piedad, Steven M. Greenberg, Helen Kim, Kelly D. Flemming, Yuan Ji, Issam A. Awad
Summary: The study aims to optimize biomarkers for accurate diagnosis of cerebral cavernous angioma with symptomatic hemorrhage (CASH), predict the risk of future hemorrhage, and monitor cases after bleeding and in response to therapy.
Article
Oncology
Zhenxing Liu, Kaikai Guo, Xuebin Hu, Xianqin Zhang
Summary: In this study, a novel heterozygous mutation (c.1159C>T, p.Q387X) in the KRIT1 gene was identified in a four-generation family with cerebral cavernous malformation (CCM). This mutation resulted in premature termination of the KRIT1 protein, providing further evidence that KRIT1 mutations are a cause of CCM. These findings are important for the treatment and genetic diagnosis of CCM.
FRONTIERS IN ONCOLOGY
(2023)
Article
Neurosciences
Guoqing Han, Li Ma, Huanhuan Qiao, Lin Han, Qiaoli Wu, Qingguo Li
Summary: Cerebral cavernous malformations (CCMs) are common vascular malformations in the central nervous system, with familial CCMs being an autosomal dominant inherited disease. This study identified a novel CCM2 gene variant in a Chinese family with multiple CCM patients, contributing to better understanding of gene mutations in CCMs.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Alejandro N. Santos, Laurel Rauschenbach, Dino Saban, Bixia Chen, Marvin Darkwah Oppong, Annika Herten, Hanah Hadice Gull, Christoph Riess, Cornelius Deuschl, Boerge Schmidt, Ramazan Jabbarli, Karsten H. Wrede, Yuan Zhu, Benedikt Frank, Ulrich Sure, Philipp Dammann
Summary: This study analyzed and compared the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM, and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. The results showed that FCCM patients with intracerebral hemorrhage (ICH) at diagnosis are prone to develop rebleeding. During the 5-year follow-up, FCCM patients and patients with sporadic multiple CCM have a similar susceptibility to (re)hemorrhage.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Gustavo da Fontoura Galvao, Elielson Veloso da Silva, Luisa Menezes Trefilio, Soniza Vieira Alves-Leon, Fabricia Lima Fontes-Dantas, Jorge Marcondes de Souza
Summary: This study investigates the clinical and genetic characteristics of two CCM3 patients, showing early onset of symptoms and a high lesion burden. Through quantitative PCR and bioinformatics analysis, the study reveals the mechanism of PDCD10 gene mutations. These findings are important for accurate diagnosis, treatment, and understanding the pathogenesis of CCM3.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Concetta Scimone, Simona Alibrandi, Luigi Donato, Giuseppe Valerio De Gaetano, Carmela Fusco, Grazia Nardella, Marco Castori, Carmela Rinaldi, Concetta Alafaci, Antonino Germano, Rosalia D'Angelo, Antonina Sidoti
Summary: In the central nervous system, thrombin-mediated activation of protease-activated receptors (PARs) results in neuroinflammation and increased vascular permeability, which have been linked to cancer and neurodegeneration. Endothelial cells (ECs) isolated from sporadic cerebral cavernous malformation (CCM) specimens showed dysregulation of genes involved in thrombin-mediated PAR-1 activation signaling. Additionally, thrombin exposure affects EC viability and results in dysregulation of CCM gene expression and decreased protein level, suggesting the possible role of PAR1-mediated thrombin signaling in sporadic CCM.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Editorial Material
Medicine, General & Internal
Aubrey C. Chan, Christopher A. Burke, Ellen M. Coffey, David R. Hilden, Diego L. Coira, Jessy Warner-Cohen, Margaret Grady, Philip R. Muskin, Gen Shinozaki
ANNALS OF INTERNAL MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
Tara M. Mleynek, Aubrey C. Chan, Michael Redd, Christopher C. Gibson, Chadwick T. Davis, Dallas S. Shi, Tiehua Chen, Kandis L. Carter, Jing Ling, Raquel Blanco, Holger Gerhardt, Kevin Whitehead, Dean Y. Li
HUMAN MOLECULAR GENETICS
(2014)
Article
Medicine, Research & Experimental
Aubrey C. Chan, Stavros G. Drakos, Oscar E. Ruiz, Alexandra C. H. Smith, Christopher C. Gibson, Jing Ling, Samuel F. Passi, Amber N. Stratman, Anastasia Sacharidou, M. Patricia Revelo, Allie H. Grossmann, Nikolaos A. Diakos, George E. Davis, Mark M. Metzstein, Kevin J. Whitehead, Dean Y. Li
JOURNAL OF CLINICAL INVESTIGATION
(2011)
Article
Cell Biology
Christopher A. Jones, Naoyuki Nishiya, Nyall R. London, Weiquan Zhu, Lise K. Sorensen, Aubrey C. Chan, Chinten J. Lim, Haoyu Chen, Qisheng Zhang, Peter G. Schultz, Alaa M. Hayallah, Kirk R. Thomas, Michael Famulok, Kang Zhang, Mark H. Ginsberg, Dean Y. Li
NATURE CELL BIOLOGY
(2009)
Correction
Biochemistry & Molecular Biology
Kevin J. Whitehead, Aubrey C. Chan, Sutip Navankasattusas, Wonshill Koh, Nyall R. London, Jing Ling, Anne H. Mayo, Stavros G. Drakos, Christopher A. Jones, Weiquan Zhu, Douglas A. Marchuk, George E. Davis, Dean Y. Li
Article
Biochemistry & Molecular Biology
Kevin J. Whitehead, Aubrey C. Chan, Sutip Navankasattusas, Wonshill Koh, Nyall R. London, Jing Ling, Anne H. Mayo, Stavros G. Drakos, Douglas A. Marchuk, George E. Davis, Dean Y. Li
Article
Clinical Neurology
Gen Shinozaki, Aubrey C. Chan, Nicholas A. Sparr, Kasra Zarei, Lindsey N. Gaul, Jonathan T. Heinzman, Julian Robles, Kumi Yuki, Theodosis J. Chronis, Timothy Ando, Terrence Wong, Sayeh Sabbagh, Michelle T. Weckmann, Sangil Lee, Thoru Yamada, Matthew D. Karam, Nicolas O. Noiseux, Eri Shinozaki, John W. Cromwell
PSYCHIATRY AND CLINICAL NEUROSCIENCES
(2018)
Article
Cell Biology
Nyall R. London, Weiquan Zhu, Fernando A. Bozza, Matthew C. P. Smith, Daniel M. Greif, Lise K. Sorensen, Luming Chen, Yuuki Kaminoh, Aubrey C. Chan, Samuel F. Passi, Craig W. Day, Dale L. Barnard, Guy A. Zimmerman, Mark A. Krasnow, Dean Y. Li
SCIENCE TRANSLATIONAL MEDICINE
(2010)
Letter
Emergency Medicine
Sangil Lee, Kumi Yuki, Aubrey Chan, John Cromwell, Gen Shinozaki
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2019)
Article
Clinical Neurology
Patricia R. Braun, Mai Tanaka-Sahker, Aubrey C. Chan, Sydney S. Jellison, Mason J. Klisares, Benjamin W. Hing, Yaseen Shabbir, Lindsey N. Gaul, Yasunori Nagahama, Julian Robles, Jonathan T. Heinzman, Sayeh Sabbagh, Ellyn M. Cramer, Gabrielle N. Duncan, Kumi Yuki, Liesl N. Close, Brian J. Dlouhy, Matthew A. Howard, Hiroto Kawasaki, Kyle M. Stein, James B. Potash, Gen Shinozaki
PSYCHIATRY AND CLINICAL NEUROSCIENCES
(2019)
Article
Behavioral Sciences
Rebecca J. Taugher, Amanda M. Wunsch, Grace Z. Wang, Aubrey C. Chan, Brian J. Dlouhy, John A. Wemmie
Summary: The exposure to carbon dioxide can enhance fear memory in a time-dependent manner. The specific enhancing effect of CO2 on fear conditioning seem to depend on the acid-sensing ion channel-1a (ASIC1A). Preventing peritraumatic acidosis may reduce the risk of developing PTSD.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Neurosciences
Gail I. S. Harmata, Aubrey C. Chan, Madison J. Merfeld, Rebecca J. Taugher-Hebl, Anjit K. Harijan, Jason B. Hardie, Rong Fan, Jeffrey D. Long, Grace Z. Wang, Brian J. Dlouhy, Amal K. Bera, Nandakumar S. Narayanan, John A. Wemmie
Summary: Individuals differ in their sensitivity to acute alcohol intoxication, and alcohol effects are complex and may be related to acid-sensing ion channels (ASICs). This study found that ASIC1A plays a role in the intoxicating effects of alcohol, and its absence affects the electrophysiological responses and behavior. These findings suggest that ASICs might contribute to the intoxicating effects of alcohol and AUD in humans.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Psychology, Clinical
Gen Shinozaki, Nicholas L. Bormann, Aubrey C. Chan, Kasra Zarei, Nicholas A. Sparr, Mason J. Klisares, Sydney S. Jellison, Jonathan T. Heinzman, Elijah B. Dahlstrom, Gabrielle N. Duncan, Lindsey N. Gaul, Robert J. Wanzek, Ellyn M. Cramer, Charlotte G. Wimmel, Sayeh Sabbagh, Kumi Yuki, Michelle T. Weckmann, Thoru Yamada, Matthew D. Karam, Nicolas O. Noiseux, Eri Shinozaki, Hyunkeun R. Cho, Sangil Lee, John W. Cromwell
JOURNAL OF CLINICAL PSYCHIATRY
(2019)
Article
Cardiac & Cardiovascular Systems
Christopher C. Gibson, Weiquan Zhu, Chadwick T. Davis, Jay A. Bowman-Kirigin, Aubrey C. Chan, Jing Ling, Ashley E. Walker, Luca Goitre, Simona Delle Monache, Saverio Francesco Retta, Yan-Ting E. Shiu, Allie H. Grossmann, Kirk R. Thomas, Anthony J. Donato, Lisa A. Lesniewski, Kevin J. Whitehead, Dean Y. Li