Matches in SemOpenAlex for { <https://semopenalex.org/work/W2955902461> ?p ?o ?g. }
- W2955902461 startingPage "690172" @default.
- W2955902461 abstract "Abstract Cyclin-dependent-like kinase 5 (Cdkl5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognised anamnestic deficiency in pain perception. Consistent with a role in nociception, we discovered that Cdkl5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in iPS-derived human nociceptors. CDKL5 deficient mice display defective epidermal innervation and conditional deletion of Cdkl5 in DRG sensory neurons significantly impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, Cdkl5 interacts with CaMKIIα to control outgrowth as well as TRPV1-dependent signalling, which are disrupted in both Cdkl5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for Cdkl5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder. One Sentence Summary Cyclin-dependent-like kinase 5 (Cdkl5) controls nociception in patients and murine models of Cdkl5 deficiency disorder via CaMKII-dependent mechanisms" @default.
- W2955902461 created "2019-07-12" @default.
- W2955902461 creator A5004742593 @default.
- W2955902461 creator A5006737481 @default.
- W2955902461 creator A5014801114 @default.
- W2955902461 creator A5016100084 @default.
- W2955902461 creator A5018015135 @default.
- W2955902461 creator A5029098899 @default.
- W2955902461 creator A5035871532 @default.
- W2955902461 creator A5038715666 @default.
- W2955902461 creator A5041387451 @default.
- W2955902461 creator A5044713075 @default.
- W2955902461 creator A5045593878 @default.
- W2955902461 creator A5050838295 @default.
- W2955902461 creator A5072800302 @default.
- W2955902461 creator A5077914603 @default.
- W2955902461 creator A5077953782 @default.
- W2955902461 creator A5087445356 @default.
- W2955902461 creator A5088800385 @default.
- W2955902461 creator A5091191421 @default.
- W2955902461 date "2019-07-02" @default.
- W2955902461 modified "2023-09-26" @default.
- W2955902461 title "Cyclin-dependent-like kinase 5 is required for pain signalling in both human neurons and mouse models" @default.
- W2955902461 cites W1501923953 @default.
- W2955902461 cites W1577345535 @default.
- W2955902461 cites W1589304766 @default.
- W2955902461 cites W1943690074 @default.
- W2955902461 cites W1968087072 @default.
- W2955902461 cites W1982644673 @default.
- W2955902461 cites W1984458059 @default.
- W2955902461 cites W1986656413 @default.
- W2955902461 cites W1989199110 @default.
- W2955902461 cites W1992745256 @default.
- W2955902461 cites W1994266757 @default.
- W2955902461 cites W1999024554 @default.
- W2955902461 cites W2010079769 @default.
- W2955902461 cites W2021211719 @default.
- W2955902461 cites W2030648771 @default.
- W2955902461 cites W2033963984 @default.
- W2955902461 cites W2035429056 @default.
- W2955902461 cites W2036741271 @default.
- W2955902461 cites W2041060940 @default.
- W2955902461 cites W2042941423 @default.
- W2955902461 cites W2049021349 @default.
- W2955902461 cites W2049868560 @default.
- W2955902461 cites W2052606529 @default.
- W2955902461 cites W2054594911 @default.
- W2955902461 cites W2057354900 @default.
- W2955902461 cites W2060255725 @default.
- W2955902461 cites W2061432570 @default.
- W2955902461 cites W2066106589 @default.
- W2955902461 cites W2068327049 @default.
- W2955902461 cites W2076018693 @default.
- W2955902461 cites W2077358692 @default.
- W2955902461 cites W2080752012 @default.
- W2955902461 cites W2082682623 @default.
- W2955902461 cites W2084522972 @default.
- W2955902461 cites W2094437785 @default.
- W2955902461 cites W2096845976 @default.
- W2955902461 cites W2101752858 @default.
- W2955902461 cites W2104568401 @default.
- W2955902461 cites W2108328978 @default.
- W2955902461 cites W2112868108 @default.
- W2955902461 cites W2118610309 @default.
- W2955902461 cites W2149522457 @default.
- W2955902461 cites W2149762749 @default.
- W2955902461 cites W2162984490 @default.
- W2955902461 cites W2165635063 @default.
- W2955902461 cites W2184461463 @default.
- W2955902461 cites W2260115926 @default.
- W2955902461 cites W2330895054 @default.
- W2955902461 cites W2335852171 @default.
- W2955902461 cites W2338814967 @default.
- W2955902461 cites W2359604401 @default.
- W2955902461 cites W2441719627 @default.
- W2955902461 cites W2496824318 @default.
- W2955902461 cites W2509047732 @default.
- W2955902461 cites W2556223017 @default.
- W2955902461 cites W2581719304 @default.
- W2955902461 cites W2582734929 @default.
- W2955902461 cites W2618702895 @default.
- W2955902461 cites W2743718080 @default.
- W2955902461 cites W2765629363 @default.
- W2955902461 cites W2774562881 @default.
- W2955902461 cites W2800672823 @default.
- W2955902461 cites W2803106339 @default.
- W2955902461 cites W2885029993 @default.
- W2955902461 cites W2892383969 @default.
- W2955902461 cites W2894366250 @default.
- W2955902461 cites W2896504526 @default.
- W2955902461 doi "https://doi.org/10.1101/690172v1" @default.
- W2955902461 hasPublicationYear "2019" @default.
- W2955902461 type Work @default.
- W2955902461 sameAs 2955902461 @default.
- W2955902461 citedByCount "0" @default.
- W2955902461 crossrefType "posted-content" @default.
- W2955902461 hasAuthorship W2955902461A5004742593 @default.
- W2955902461 hasAuthorship W2955902461A5006737481 @default.
- W2955902461 hasAuthorship W2955902461A5014801114 @default.