Elsevier

Neuroscience Research

Volume 69, Issue 4, April 2011, Pages 343-347
Neuroscience Research

Rapid communication
mRNA distribution of the thalidomide binding protein cereblon in adult mouse brain

https://doi.org/10.1016/j.neures.2010.12.019Get rights and content

Abstract

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.

Research highlights

▶ All brain neurons express cereblon mRNA with various intensities. ▶ Glial expression of cereblon mRNA is limited. ▶ Cereblon mRNA levels are the highest in hippocampal pyramidal cells and cerebellar Purkinje cells. ▶ Cereblon mRNA is enriched in serotonergic and noradrenergic neurons as well.

Section snippets

Acknowledgements

This work was supported by the Basic Scientific Research (B), the Health and Labor Sciences Research Grants, a grant for Promotion of Niigata University Research Projects, and Core Research for Evolutional Science and Technology from the JST Corporation.

References (22)

  • T. Eriksson et al.

    Clinical pharmacology of thalidomide

    Eur. J. Clin. Pharmacol.

    (2001)
  • Cited by (18)

    • The Ubiquitination-Dependent and -Independent Functions of Cereblon in Cancer and Neurological Diseases

      2022, Journal of Molecular Biology
      Citation Excerpt :

      The human protein cereblon (CRBN, UniProt accession #: Q96SW2) contains 442 amino acids and consists of a Lon-N-terminal domain without the ATP-binding and catalytic domains at its N terminus, and an IMiD-binding motif at its C terminus (Figure 1(A)).19 It is highly expressed in cerebellum and plays important roles in cerebral development.20,21 Hence, it is named as cereblon.

    • Exploiting ubiquitin ligase cereblon as a target for small-molecule compounds in medicine and chemical biology

      2021, Cell Chemical Biology
      Citation Excerpt :

      As mentioned above, mutations of human CRBN are associated with intellectual disability, implying that CRBN plays a role in brain function. Rodent Crbn is widely expressed in post-mitotic neurons in the adult brain, including the hippocampus, cerebellum, and cortex (Aizawa et al., 2011). In 2012, germ line Crbn-deficient mice and forebrain-specific Crbn-deficient mice were established (Rajadhyaksha et al., 2012).

    • Cereblon Control of Zebrafish Brain Size by Regulation of Neural Stem Cell Proliferation

      2019, iScience
      Citation Excerpt :

      DDB1, one of the subunits of CRL4CRBN, is required for cell proliferation through the p53-dependent pathway in the developing brain (Cang et al., 2006; Hu et al., 2015). Coincidentally, CRBN was originally reported as a gene responsible for autosomal recessive, non-syndromic mental retardation in humans (Higgins et al., 2004) and is highly expressed in the vertebrate brain (Higgins et al., 2010; Aizawa et al., 2011). In addition, it has been reported that CRBN also regulates the expression of functional large-conductance, Ca2+- and voltage-activated K+ (BK) channels, which are involved in neuronal excitability and epileptogenesis (Jo et al., 2005; Liu et al., 2014).

    • Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma

      2018, Blood Advances
      Citation Excerpt :

      We and others reported single-agent activity of lenalidomide in refractory secondary CNS diffuse large B-cell lymphoma (DLBCL) as well as mantle cell lymphoma involving the CNS.18,19 Given reports of neurotoxicity associated with lenalidomide and other immunomodulatory drugs in the setting of myeloma and other lymphoid malignancies,20,21 that the direct binding protein and mediator of cellular activity of lenalidomide, cereblon, is highly expressed in neurons in the brain,22,23 and that it is well-established that CNS lymphoma patients are at high risk for neurocognitive deficits and neurotoxicity, we designed a phase 1 investigation to determine a safe, maximum tolerated dose (MTD) of lenalidomide for this patient population. The rationale for this approach is also supported by the fact that CNS lymphoma patients often have a poor performance status and are particularly vulnerable because of immune suppression.

    View all citing articles on Scopus
    View full text