Imperial College London
Alternate

DrIstvanNagy

Faculty of Medicine, Department of Surgery & Cancer

Reader in Nociceptive Mechanisms
 
 
 
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Contact

 

+44 (0)20 3315 8897i.nagy Website

 
 
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Assistant

 

Miss Steffi Klier +44 (0)20 3315 8816

 
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Location

 

G345Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{La:2020:10.1126/scitranslmed.aax4846,
author = {La, Montanara P and Hervera, A and Baltussen, L and Hutson, TH and Palmisano, I and De, Virgiliis F and Gao, Y and Bartus, K and Majid, Q and Gorgoraptis, N and Wong, K and Downs, J and Pizzorusso, T and Ultanir, S and Leonard, H and Yu, H and Millar, DS and Nagy, I and Mazarakis, N and Di, Giovanni S},
doi = {10.1126/scitranslmed.aax4846},
journal = {Science Translational Medicine},
pages = {1--11},
title = {Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models},
url = {http://dx.doi.org/10.1126/scitranslmed.aax4846},
volume = {12},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - La,Montanara P
AU  - Hervera,A
AU  - Baltussen,L
AU  - Hutson,TH
AU  - Palmisano,I
AU  - De,Virgiliis F
AU  - Gao,Y
AU  - Bartus,K
AU  - Majid,Q
AU  - Gorgoraptis,N
AU  - Wong,K
AU  - Downs,J
AU  - Pizzorusso,T
AU  - Ultanir,S
AU  - Leonard,H
AU  - Yu,H
AU  - Millar,DS
AU  - Nagy,I
AU  - Mazarakis,N
AU  - Di,Giovanni S
DO  - 10.1126/scitranslmed.aax4846
EP  - 11
PY  - 2020///
SN  - 1946-6234
SP  - 1
TI  - Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models
T2  - Science Translational Medicine
UR  - http://dx.doi.org/10.1126/scitranslmed.aax4846
UR  - http://hdl.handle.net/10044/1/80641
VL  - 12
ER  -
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