Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum neurotoxin type-A (BoNT-A) is clinically used for patients with pain disorders and dystonia. The precise mechanism whereby BoNT-A controls pain remains elusive. Here, we studied how BoNT-A affects the expression of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a cation channel critically implicated in nociception, in the trigeminal system. Histological studies revealed that subcutaneous BoNT-A injection (0.25, 0.5, or 5 ng/kg) into the face targeted the ophthalmic division of trigeminal ganglion (TG) neurons and decreased TRPV1-immunoreactive neurons in the TG and TRPV1-immunoreactive fibers in rat trigeminal terminals. Of note, TG neurons that received projections from the dura mater, a principal site of headache generation, had reduced TRPV1 expression. BoNT-A-induced cleavage of SNAP25 (synaptosomal-associated protein of 25-kDa) in the TG became obvious 2 days after BoNT-A administration and persisted for at least 14 days. Quantitative real-time RT-PCR (reverse transcription-polymerase chain reaction) data indicated that the TRPV1-decreasing effects of BoNT-A were not mediated by transcriptional downregulation. By employing a surface protein biotin-labeling assay, we demonstrated that BoNT-A inhibited TRPV1 trafficking to the plasma membrane in primary TG neurons. Moreover, Y200F-mutated TRPV1, which is incapable of trafficking to the plasma membrane, was expressed in PC12 cells by transfection, and pharmacological studies revealed that TRPV1 in the cytoplasm was more predisposed to proteasome-mediated proteolysis than plasma membrane-located TRPV1. We conclude that the mechanism by which BoNT-A reduces TRPV1 expression involves the inhibition of TRPV1 plasma membrane trafficking and proteasome-mediated degradation in the cytoplasm. This paradigm seems to explain how BoNT-A alleviates TRPV1-mediated pain. Our data reveal a likely molecular mechanism whereby BoNT-A treatment reduces TRPV1 expression in the trigeminal system and provide important clues to novel therapeutic measures for ameliorating craniofacial pain.
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PMID:Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A. 2282 Jan 41

Background: Multiple intracranial meningiomas account for <10% of all meningiomas. Familial multiple meningiomas have been linked to germline mutations in two genes: neurofibromatosis type 2 (NF2) and SWIch/Sucrose Non-Fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1). Sporadic multiple meningiomas have been associated with somatic NF2 mutations and, to date, there has been no case related to somatic SMARCB1 mutations. Here, we describe the first case. Case Report: A 45-year-old female suffered a head trauma while snowboarding. Subsequent to her injury, she experienced persistent headache, nausea, vomiting, dizziness, and flashing lights in the right eye. Magnetic resonance imaging (MRI) of her brain revealed multiple intracranial meningiomas. She underwent a two-staged craniotomy to remove frontal/parietal/temporal and occipital extra-axial tumors. Pathology confirmed the masses as meningiomas, WHO Grade I. Tumor genetic testing was positive for SMARCB1 mutation but blood genetic testing was negative for SMARCB1 mutation. Conclusion: In sporadic multiple meningiomas, somatic NF2 mutations are usually the suspected genetic alternations. Our case illustrates that somatic SMARCB1 mutation is another genetic risk factor for sporadic multiple meningiomas, albeit rare.
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PMID:Somatic SMARCB1 Mutation in Sporadic Multiple Meningiomas: Case Report. 3041 84