CRMP2 is necessary for Neurofibromatosis type 1 related pain

Channels
Aubin MoutalRajesh Khanna

Abstract

Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases, affecting roughly 1 in 3000 individuals. As a multisystem disorder, it affects cognitive development, as well as bone, nerve and muscle constitution. Peripheral neuropathy in NF1 constitutes a potentially severe clinical complication and is associated with increased morbidity and mortality. The discovery of effective therapies for Neurofibromatosis type 1 (NF1) pain depends on mechanistic understanding that has been limited, in part, by the relative lack of availability of animal models relevant to NF1 pain. We have used intrathecal targeted editing of Nf1 in rats to provide direct evidence of a causal relationship between neurofibromin and pain responses. We demonstrated that editing of neurofibromin results in functional remodeling of peripheral nociceptors characterized by enhancement of interactions of the tetrodotoxin-sensitive (TTX-S) Na+ voltage-gated sodium channel (NaV1.7) and the collapsin response mediator protein 2 (CRMP2). Collectively, these peripheral adaptations increase sensory neuron excitability and release of excitatory transmitters to the spinal dorsal horn to establish and maintain a state of central sensitization reflected by hyper...Continue Reading

References

Mar 27, 1999·Brain : a Journal of Neurology·A CréangePierre Wolkenstein
Aug 4, 2004·Brain : a Journal of Neurology·Alain DrouetAlain Créange
Aug 30, 2007·American Journal of Medical Genetics. Part a·Robert B NollCynthia A Gerhardt
Nov 21, 2012·Developmental Medicine and Child Neurology·Shruti GargJonathan Green
Nov 21, 2012·Developmental Medicine and Child Neurology·Karin S WalshMaria T Acosta
Nov 6, 2013·Pediatrics·Shruti GargSusan M Huson
Sep 23, 2014·Nature Neuroscience·Andrei I MoloshAnantha Shekhar
Dec 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Erik T DustrudeRajesh Khanna
May 24, 2017·Molecular Psychiatry·Aubin MoutalRajesh Khanna

Citations

Mar 28, 2019·Molecular Neurobiology·Aubin MoutalRajesh Khanna
Aug 29, 2019·Molecular Brain·Agustin Garcia-CaballeroGerald W Zamponi
Nov 5, 2019·Channels·Aubin MoutalRajesh Khanna
Jun 22, 2018·JCI Insight·Katherine A WhiteJill M Weimer
Oct 27, 2018·Neuronal Signaling·Lindsey A Chew, Rajesh Khanna
Dec 20, 2018·Molecular Neurobiology·Jie YuRajesh Khanna
Aug 11, 2020·Pain·Kimberly GomezRajesh Khanna
Dec 29, 2020·Neurobiology of Disease·Chinnasamy DhanalakshmiMark A Nelson
Jul 26, 2019·Neurobiology of Disease·Udaiyappan JanakiramanMark A Nelson
Apr 16, 2018·Neuroscience·Aubin MoutalRajesh Khanna

Methods Mentioned

BETA
GTPase
transfection

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