Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P01185 (
vasopressin
)
23,126
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thalidomide exerts its teratogenic and immunomodulatory effects by binding to
cereblon
(
CRBN
) and thereby inhibiting/modifying the
CRBN
-mediated ubiquitination pathway consisting of the Cullin4-DDB1-ROC1 E3 ligase complex. The mechanism of thalidomide's classical hypnotic effect remains largely unexplored, however. Here we examined whether
CRBN
is involved in the hypnotic effect of thalidomide by generating mice harboring a thalidomide-resistant mutant allele of
Crbn
(
Crbn YW/AA
knock-in mice). Thalidomide increased non-REM sleep time in
Crbn YW/AA
knock-in homozygotes and heterozygotes to a similar degree as seen in wild-type littermates. Thalidomide similarly depressed excitatory synaptic transmission in the cortical slices obtained from wild-type and
Crbn YW/AA
homozygous knock-in mice without affecting GABAergic inhibition. Thalidomide induced Fos expression in
vasopressin
-containing neurons of the supraoptic nucleus and reduced Fos expression in the tuberomammillary nuclei. Thus, thalidomide's hypnotic effect seems to share some downstream mechanisms with general anesthetics and GABA
A
-activating sedatives but does not involve the teratogenic
CRBN
-mediated ubiquitin/proteasome pathway.
...
PMID:Hypnotic effect of thalidomide is independent of teratogenic ubiquitin/proteasome pathway. 3284 52
