A mechanistic review on GNAO1-associated movement disorder

Neurobiology of Disease
Huijie FengChristos Sidiropoulos

Abstract

Mutations in the GNAO1 gene cause a complex constellation of neurological disorders including epilepsy, developmental delay, and movement disorders. GNAO1 encodes Gαo, the α subunit of Go, a member of the Gi/o family of heterotrimeric G protein signal transducers. Go is the most abundant membrane protein in the mammalian central nervous system and plays major roles in synaptic neurotransmission and neurodevelopment. GNAO1 mutations were first reported in early infantile epileptic encephalopathy 17 (EIEE17) but are also associated with a more common syndrome termed neurodevelopmental disorder with involuntary movements (NEDIM). Here we review a mechanistic model in which loss-of-function (LOF) GNAO1 alleles cause epilepsy and gain-of-function (GOF) alleles are primarily associated with movement disorders. We also develop a signaling framework related to cyclic AMP (cAMP), synaptic vesicle release, and neural development and discuss gene mutations perturbing those mechanisms in a range of genetic movement disorders. Finally, we analyze clinical reports of patients carrying GNAO1 mutations with respect to their symptom onset and discuss pharmacological/surgical treatments in the context of our mechanistic model.

Citations

May 8, 2019·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·Guang-Xin EYan-Bin Zhu
Feb 9, 2020·Neurology·Travis LarshHubert Fernandez
Jun 14, 2019·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Maria João MalaquiasMarina Magalhães
Aug 11, 2020·Journal of Neural Transmission·José Fidel Baizabal-Carvallo, Francisco Cardoso
Oct 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Satoshi AkamineShouichi Ohga
Oct 23, 2020·Expert Review of Neurotherapeutics·Cécile DelormeEmmanuel Roze
Dec 11, 2020·Orphanet Journal of Rare Diseases·Soo Yeon KimJong-Hee Chae
Jan 3, 2021·Journal of Neural Transmission·Paulina Gonzalez-LatapiNiccolò E Mencacci
May 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Alena Randáková, Jan Jakubík
Jun 15, 2021·Frontiers in Neurology·Xiaoling YangYuehua Zhang
Sep 12, 2021·Human Molecular Genetics·Dandan WangBrock Grill

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