Molecular and cellular approaches to cognitive impairments associated with NF1 and other rasopathies

Yong-Seok Lee, Alcino J. Silva

Research output: Chapter in Book/Report/Conference proceedingChapterResearchpeer-review

Abstract

Neurofibromatosis type 1 (NF1) is a single-gene disorder with multiple somatic and behavioral phenotypes. NF1 and other related disorders, including Noonan syndrome, Costello syndrome, LEOPARD syndrome, and CFC syndrome are caused by gain-of-function mutations in various components of the Ras-MAPK signaling pathway and are therefore known as rasopathies. Individuals affected with any one of these disorders exhibit various cognitive problems such as learning disabilities and mental retardation. Many of the cognitive phenotypes observed in the rasopathies can be modeled in animal models, including mice. Studies in these animal models have played an important role in understanding the molecular and cellular mechanisms underlying the cognitive deficits associated with NF1 and other rasopathies. For example, studies in mouse models of NF1 have shown that increased inhibition and subsequent disruptions in synaptic plasticity caused by increased Ras signaling are responsible for cognitive deficits in this condition. Based on these mechanistic findings, pharmacological interventions that decrease Ras signaling have been shown to be able to rescue deficits in both synaptic plasticity and behavior in a mouse model of NF1, and these have inspired current clinical trials. In this chapter, we shall review molecular, cellular, and behavioral studies of mouse models of NF1 and other rasopathies, as well as efforts to use these results to develop treatments for this class of conditions.

Original languageEnglish
Title of host publicationNeurofibromatosis Type 1
Subtitle of host publicationMolecular and Cellular Biology
PublisherSpringer-Verlag Berlin Heidelberg
Pages569-588
Number of pages20
Volume9783642328640
ISBN (Electronic)9783642328640
ISBN (Print)3642328636, 9783642328633
DOIs
StatePublished - 1 Aug 2012

Fingerprint

Neurofibromatosis 1
Neuronal Plasticity
Plasticity
Animals
Costello Syndrome
LEOPARD Syndrome
Animal Models
Chlorofluorocarbons
Noonan Syndrome
Phenotype
Learning Disorders
Intellectual Disability
Genes
Cognitive Dysfunction
Clinical Trials
Pharmacology
Mutation

Cite this

Lee, Y-S., & Silva, A. J. (2012). Molecular and cellular approaches to cognitive impairments associated with NF1 and other rasopathies. In Neurofibromatosis Type 1: Molecular and Cellular Biology (Vol. 9783642328640, pp. 569-588). Springer-Verlag Berlin Heidelberg. https://doi.org/10.1007/978-3-642-32864-0_37
Lee, Yong-Seok ; Silva, Alcino J. / Molecular and cellular approaches to cognitive impairments associated with NF1 and other rasopathies. Neurofibromatosis Type 1: Molecular and Cellular Biology. Vol. 9783642328640 Springer-Verlag Berlin Heidelberg, 2012. pp. 569-588
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Lee, Y-S & Silva, AJ 2012, Molecular and cellular approaches to cognitive impairments associated with NF1 and other rasopathies. in Neurofibromatosis Type 1: Molecular and Cellular Biology. vol. 9783642328640, Springer-Verlag Berlin Heidelberg, pp. 569-588. https://doi.org/10.1007/978-3-642-32864-0_37

Molecular and cellular approaches to cognitive impairments associated with NF1 and other rasopathies. / Lee, Yong-Seok; Silva, Alcino J.

Neurofibromatosis Type 1: Molecular and Cellular Biology. Vol. 9783642328640 Springer-Verlag Berlin Heidelberg, 2012. p. 569-588.

Research output: Chapter in Book/Report/Conference proceedingChapterResearchpeer-review

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Lee Y-S, Silva AJ. Molecular and cellular approaches to cognitive impairments associated with NF1 and other rasopathies. In Neurofibromatosis Type 1: Molecular and Cellular Biology. Vol. 9783642328640. Springer-Verlag Berlin Heidelberg. 2012. p. 569-588 https://doi.org/10.1007/978-3-642-32864-0_37