Journal
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
Volume 36, Issue 10, Pages 2206-2213Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2012.07.008
Keywords
Timothy syndrome; SYNGAP1; ERK1; Circadian rhythm
Categories
Ask authors/readers for more resources
Signal transduction from the synapse to the nucleus subsequently involves transient increases in synaptic Ca2+, activation of CaM kinases, activation of the GTPase Ras, activation of the ERK mitogen-activated protein kinase pathway, and finally GSK3 inhibition and CREB-activation. Genetic studies in autism have identified mutations and copy number variations in a number of genes involved in this synapse to nucleus signaling path. In particular, a gain of function mutation in the CACNA1C gene, deletions and disruption of the SYNGAP1 gene, a copy number variation encompassing the MAPK3 gene and a duplication of YWHAE indicate that in a subset of autism patients the ERK cascade is inappropriately activated. Predicted functional consequences of this hyperactivation would be an increase in complexity of the dendritic tree, and via inhibition of GSK3, a delayed circadian phase. The latter effect indeed fits the frequent sleep disturbances observed in autistic patients. Interestingly, the sleep disturbances in bipolar disorder patients are frequently characterized as phase advanced. A selective evaluation of genetic mutations in bipolar patients indicates that the activity of the ERK cascade, at least in a subset of patients, presumably is hypoactive. Thus, with respect to the ERK pathway, autism and bipolar disorder seem each other's counter pole. (C) 2012 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available