Accession Number : ADA583362


Title :   Characterization of an E3 Ubiquitin Ligase that Degrades Neurofibromin in Vitro and Vivo


Descriptive Note : Annual rept. 1 Apr 2011-31 Mar 2012


Corporate Author : MICHIGAN UNIV ANN ARBOR


Personal Author(s) : Zhu, Yuan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a583362.pdf


Report Date : Apr 2012


Pagination or Media Count : 93


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.


Descriptors :   *CENTRAL NERVOUS SYSTEM , *CLINICAL MEDICINE , *IN VITRO ANALYSIS , *IN VIVO ANALYSIS , *STEM CELLS , ANATOMICAL MODELS , BONES , BRAIN , CEREBRAL CORTEX , DEFICIENCIES , DISEASES , HYPOTHESES , LESIONS , LOOPS , MOLECULAR PROPERTIES , NEOPLASMS , PERIPHERAL NERVOUS SYSTEM , PERIPHERAL NEUROPATHY , SIGNS AND SYMPTOMS , TEST AND EVALUATION , THERAPY


Subject Categories : Medicine and Medical Research
      Stress Physiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE