Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1.

TitleMolecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1.
Publication TypeJournal Article
Year of Publication2002
AuthorsCosta, RM, Silva AJ
JournalJournal of child neurology
Volume17
Issue8
Pagination622-6; discussion 627-9, 646-51
Date Published2002 Aug
ISSN0883-0738
KeywordsAnimals, Child, Disease Models, Animal, DNA Mutational Analysis, Humans, intellectual disability, Learning Disorders, Mice, Mice, Neurologic Mutants, Neurofibromatosis 1, Neurofibromin 1
Abstract

Neurofibromatosis 1 is one of the most common single-gene disorders affecting neurologic function in humans. Mutations in the NF1 gene cause abnormalities in cell growth and differentiation and lead to a variety of learning disabilities. Neurofibromin has several biochemical functions, such as Ras-guanosine triphosphatase activity, adenylate cyclase modulation, and microtubule binding, all of which could be critical for brain function. We review how studies in mouse models are helping to unravel the molecular and cellular mechanisms underlying cognitive deficits in neurofibromatosis 1. These studies suggest that the learning disabilities associated with neurofibromatosis 1 are caused by excessive Ras activity that leads to increased gamma-aminobutyric acid (GABA(A)) inhibition and to decreased long-term potentiation. These findings have brought us closer than ever to the development of possible treatments for the learning disabilities associated with neurofibromatosis 1.

Alternate JournalJ. Child Neurol.