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Accession Number ADA583362
Title Characterization of an E3 Ubiquitin Ligase that Degrades Neurofibromin in Vitro and Vivo.
Publication Date Apr 2012
Media Count 93p
Personal Author Y. Zhu
Abstract Neurofibromatosis type 1 (NF1) patients are predisposed to various clinical complications, including benign and malignant tumors in both the peripheral nervous system and central nervous system. Furthermore, Nf1 patients are at high risks for non- tumor related symptoms such as neurocognitive and motor deficits, structural brain defects and bone abnormalities. The proposed studies attempt to provide important insights into one of the critical questions in the field of NF1 molecular mechanisms regulating neurofibromin degradation. The objectives of this proposal are to utilize a newly established mouse model to (1) elucidate a positive feedback loop in the FBXW7/NF1/ERK axis in vivo and to (2) seek novel therapeutic strategies for NF1 haploinsufficient lesions various clinical manifestations. To test this model, we propose two hypotheses: (1) Neurofibromin is an SCFFbxw7 substrate in vivo and (2) a high level of Erk activation is a specific context contributing to Nf1 haploinsufficient diseases. We propose the following two specific aims to test these hypotheses.
Keywords Anatomical models
Central nervous system
Cerebral cortex
Clinical medicine
Cognitive dysfunction
Deep- and upper-layer neurons
In vitro analysis
In vivo analysis
Intermediate progenitor cells
Molecular properties
Neural stem cells
Nf1(Neurofibromatosis type 1)
Peripheral nervous system
Peripheral neuropathy
Signs and symptoms
Stem cells
Test and evaluation

Source Agency Non Paid ADAS
NTIS Subject Category 57E - Clinical Medicine
57W - Stress Physiology
Corporate Author Michigan Univ., Ann Arbor.
Document Type Technical report
Title Note Annual rept. 1 Apr 2011-31 Mar 2012.
NTIS Issue Number 1401
Contract Number W81XWH-11-1-0251

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