Cereblon is implicated in mild mental retardation and proved to bind to a teratogenic hypnotic, thalidomide. Here, we determined cereblon mRNA distributions in adult mouse brain. Almost all neurons expressed cereblon mRNA with various intensities whereas the signals in astrocytes and oligodendrocytes were modest or negligible. Intense mRNA signals were found in the hippocampus and cerebellum, especially in hippocampal pyramidal cells and Purkinje cells. Higher levels of cereblon mRNA were also detected in serotonergic and noradrenergic neurons in raphe nuclei and locus ceruleus, respectively. These observations indicate novel biological roles of cereblon in neuronal physiology and thalidomide pharmacology.
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http://dx.doi.org/10.1016/j.neures.2010.12.019 | DOI Listing |
Cell Death Dis
August 2024
Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe, Japan.
Int J Gen Med
November 2023
Department of Critical Care Medicine, Ganzhou People's Hospital, Ganzhou, Jiangxi Province, 341000, People's Republic of China.
Objective: To investigate the correlation between the expression of cereblon (CRBN) protein in peripheral blood and the severity and prognosis of sepsis.
Methods: A total of 130 patients with sepsis admitted to our hospital were selected as the observation subjects (sepsis group). The patients were divided into mild group, moderate group and severe group according to their conditions.
PLoS One
November 2023
Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Stockholm, Sweden.
The retinoblastoma protein (Rb) is encoded by the RB1 tumor suppressor gene. Inactivation of RB1 by inherited or somatic mutation occurs in retinoblastoma and various other types of tumors. A significant fraction (25.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2023
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
Thalidomide has a dark history as a teratogen, but in recent years, its derivates have been shown to function as potent chemotherapeutic agents. These drugs bind cereblon (CRBN), the substrate receptor of an E3 ubiquitin ligase complex, and modify its degradation targets. Despite these insights, remarkably little is known about the normal function of cereblon in development.
View Article and Find Full Text PDFEur J Med Chem
November 2023
Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address:
As a critical upstream regulator of nuclear factor-κB (NF-κB) activation, Bruton's tyrosine kinase (BTK) has been identified to be an effective therapeutic target for the treatment of acute or chronic inflammatory diseases. Herein, we describe the design, synthesis and structure-activity-relationship analysis of a novel series of Ibrutinib-based BTK PROTACs by recruiting Cereblon (CRBN) ligase. Among them, compound 15 was identified as the most potent degrader with a DC of 3.
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