Details

Autor(en) / Beteiligte

• Borrie, Sarah C
• Brems, Hilde
• Legius, Eric
• Bagni, Claudia

Titel

Cognitive Dysfunctions in Intellectual Disabilities: The Contributions of the Ras-MAPK and PI3K-AKT-mTOR Pathways

Ist Teil von

• Annual review of genomics and human genetics, 2017-08, Vol.18 (1), p.115-142

Ort / Verlag

United States: Annual Reviews

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The Ras-MAPK and PI3K-AKT-mTOR signaling cascades were originally identified as cancer regulatory pathways but have now been demonstrated to be critical for synaptic plasticity and behavior. Neurodevelopmental disorders arising from mutations in these pathways exhibit related neurological phenotypes, including cognitive dysfunction, autism, and intellectual disability. The downstream targets of these pathways include regulation of transcription and protein synthesis. Other disorders that affect protein translation include fragile X syndrome (an important cause of syndromal autism), and other translational regulators are now also linked to autism. Here, we review how mechanisms of synaptic plasticity have been revealed by studies of mouse models for Ras-MAPK, PI3K-AKT-mTOR, and translation regulatory pathway disorders. We discuss the face validity of these mouse models and review current progress in clinical trials directed at ameliorating cognitive and behavioral symptoms.