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The Role of CNTNAP2 in Itch Sensation

      Itch is a hallmark symptom associated with atopic dermatitis (AD), which is an allergic disorder accentuated by both immunological dysregulation and epidermal barrier defect (
      • Wahlgren C.F.
      Itch and atopic dermatitis: clinical and experimental studies.
      ). Autism spectrum disorders (ASDs) are complex neurobehavioral and neurodevelopmental conditions that cause a variety of phenotypes, including impaired social communication, stereotyped behaviors, and altered sensory processing (
      • Dawes J.M.
      • Weir G.A.
      • Middleton S.J.
      • Patel R.
      • Chisholm K.I.
      • Pettingill P.
      • et al.
      Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability.
      ;
      • Vahia V.N.
      Diagnostic and statistical manual of mental disorders 5: a quick glance.
      ). A longitudinal study and a systemic review reveal an association between early AD and subsequent ASD (
      • Lee C.Y.
      • Chen M.H.
      • Jeng M.J.
      • Hsu J.W.
      • Tsai S.J.
      • Bai Y.M.
      • et al.
      Longitudinal association between early atopic dermatitis and subsequent attention-deficit or autistic disorder: a population-based case-control study.
      ;
      • Tongo M.
      • Dorfman J.R.
      • Abrahams M.R.
      • Mpoudi-Ngole E.
      • Burgers W.A.
      • Martin D.P.
      Near full-length HIV type 1M genomic sequences from Cameroon : evidence of early diverging under-sampled lineages in the country.
      ), but how itch is regulated in individuals with ASD remains unknown. In addition, excessive itching leads to sleep disorders, which accentuate neuropsychiatric illness (
      • Mazzone L.
      • Postorino V.
      • Siracusano M.
      • Riccioni A.
      • Curatolo P.
      The relationship between sleep problems, neurobiological alterations, core symptoms of autism spectrum disorder, and psychiatric comorbidities.
      ).

      Abbreviations:

      AD (atopic dermatitis), AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), ASD (autism spectrum disorder), CQ (chloroquine), KO (knockout)
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      References

        • Dawes J.M.
        • Weir G.A.
        • Middleton S.J.
        • Patel R.
        • Chisholm K.I.
        • Pettingill P.
        • et al.
        Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability.
        Neuron. 2018; 97: 806-822.e10
        • Dong X.
        • Dong X.
        Peripheral and central mechanisms of itch.
        Neuron. 2018; 98: 482-494
        • Fernandes D.
        • Santos S.D.
        • Coutinho E.
        • Whitt J.L.
        • Beltrão N.
        • Rondão T.
        • et al.
        Disrupted AMPA receptor function upon genetic- or antibody-mediated loss of autism-associated CASPR2.
        Cereb Cortex. 2019; 29: 4919-4931
        • Kaczor A.A.
        • Matosiuk D.
        Molecular structure of ionotropic glutamate receptors.
        Curr Med Chem. 2010; 17: 2608-2635
        • Kiguchi N.
        • Uta D.
        • Ding H.
        • Uchida H.
        • Saika F.
        • Matsuzaki S.
        • et al.
        GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn.
        Neuropharmacology. 2020; 170: 108025
        • Lee C.Y.
        • Chen M.H.
        • Jeng M.J.
        • Hsu J.W.
        • Tsai S.J.
        • Bai Y.M.
        • et al.
        Longitudinal association between early atopic dermatitis and subsequent attention-deficit or autistic disorder: a population-based case-control study.
        Medicine (Baltimore). 2016; 95: e5005
        • Mazzone L.
        • Postorino V.
        • Siracusano M.
        • Riccioni A.
        • Curatolo P.
        The relationship between sleep problems, neurobiological alterations, core symptoms of autism spectrum disorder, and psychiatric comorbidities.
        J Clin Med. 2018; 7: 102
        • Mishra S.K.
        • Hoon M.A.
        The cells and circuitry for itch responses in mice.
        Science. 2013; 340: 968-971
        • Peñagarikano O.
        • Abrahams B.S.
        • Herman E.I.
        • Winden K.D.
        • Gdalyahu A.
        • Dong H.
        • et al.
        Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits.
        Cell. 2011; 147: 235-246
        • Sacai H.
        • Sakoori K.
        • Konno K.
        • Nagahama K.
        • Suzuki H.
        • Watanabe T.
        • et al.
        Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex.
        Nat Commun. 2020; 11: 5140
        • Tongo M.
        • Dorfman J.R.
        • Abrahams M.R.
        • Mpoudi-Ngole E.
        • Burgers W.A.
        • Martin D.P.
        Near full-length HIV type 1M genomic sequences from Cameroon : evidence of early diverging under-sampled lineages in the country.
        Evol Med Public Health. 2015; 2015: 254-265
        • Vahia V.N.
        Diagnostic and statistical manual of mental disorders 5: a quick glance.
        Indian J Psychiatry. 2013; 55: 220-223
        • Wahlgren C.F.
        Itch and atopic dermatitis: clinical and experimental studies.
        Acta Derm Venereol Suppl (Stockh). 1991; 165: 1-53
        • Xing X.
        • Wu K.
        • Dong Y.
        • Zhou Y.
        • Zhang J.
        • Jiang F.
        • et al.
        Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice.
        Neuropharmacology. 2020; 165: 107816
        • Zou Y.
        • Zhang W.F.
        • Liu H.Y.
        • Li X.
        • Zhang X.
        • Ma X.F.
        • et al.
        Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases.
        Neural Regen Res. 2017; 12: 1551-1558
        • Zweier C.
        Severe intellectual disability associated with recessive defects in CNTNAP2 and NRXN1.
        Mol Syndromol. 2012; 2: 181-185