Imperial College London
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ProfessorNicholasMazarakis

Faculty of Medicine, Department of Brain Sciences

Chair MolBioMedicine and Head of Gene Therapy
 
 
 
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Contact

 

+44 (0)20 7594 7024n.mazarakis Website

 
 
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Assistant

 

Mrs Hadeel Abdeen +44 (0)20 7594 7014

 
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Location

 

E402Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{La:2019:10.1101/690172,
author = {La, Montanara P and Hervera, A and Baltussen, L and Hutson, T and Palmisano, I and Palmisano, I and De, Virgiliis F and Gao, Y and Majid, Q and Gorgoraptis, N and Wong, K and Downs, J and Di, Lazzaro V and Pizzorusso, T and Ultanir, S and Leonard, H and Istvan, N and Mazarakis, N and Di, Giovanni S},
doi = {10.1101/690172},
publisher = {bioRxiv},
title = {Cyclin-dependent-like kinase 5 is required for pain signalling in both human neurons and mouse models},
url = {http://dx.doi.org/10.1101/690172},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - 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
AU  - La,Montanara P
AU  - Hervera,A
AU  - Baltussen,L
AU  - Hutson,T
AU  - Palmisano,I
AU  - Palmisano,I
AU  - De,Virgiliis F
AU  - Gao,Y
AU  - Majid,Q
AU  - Gorgoraptis,N
AU  - Wong,K
AU  - Downs,J
AU  - Di,Lazzaro V
AU  - Pizzorusso,T
AU  - Ultanir,S
AU  - Leonard,H
AU  - Istvan,N
AU  - Mazarakis,N
AU  - Di,Giovanni S
DO  - 10.1101/690172
PB  - bioRxiv
PY  - 2019///
TI  - Cyclin-dependent-like kinase 5 is required for pain signalling in both human neurons and mouse models
UR  - http://dx.doi.org/10.1101/690172
UR  - https://www.biorxiv.org/content/10.1101/690172v1
UR  - http://hdl.handle.net/10044/1/78031
ER  -
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