PolyQ mutant AR/SBMAProject reference: 300723
Funded under :
SBMA as a model of polyglutamine diseases: generation of a suitable cell system to study the post-transcriptional modifications of mutant androgen receptor and to discover potential therapeutic drugs
Total cost:EUR 178 760,7
EU contribution:EUR 178 760,7
Topic(s):FP7-PEOPLE-2011-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development"
Call for proposal:FP7-PEOPLE-2011-IOFSee other projects for this call
Funding scheme:MC-IOF - International Outgoing Fellowships (IOF)
Accumulation of toxic aggregation-prone protein into inclusions and aggregates is the hallmark of most neurodegenerative diseases, a broad class of disorders including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and polyglutamine diseases. In this proposal, using SBMA as a model of neurodegenerative polyglutamine-related disorder, we intend to move a step forward expanding knowledge of the neurodegeneration. In particular, we will provide a suitable model system such as differentiated iPSCs from SBMA patients to study molecular mechanism and to find out potential therapeutic drugs for neurodegenerative diseases. To define the disease-phenotype of differentiated iPS cells we will take advantage of specific features of SBMA disorders: the ligand-dependent toxicity of expanded AR. The ligand binding induces many modifications of AR protein such as phosphorylation. Since phosphorylation of mutant AR is an important determinant of SBMA pathogenesis, we will also characterize the impact of cyclic adenosine monophosphatate (cAMP)-dependent protein kinase A (PKA) signaling on the mutant AR toxicity. Then, we will use this information to identify agents that promote such modifications to find out potential therapy. Therefore, in order to develop treatment for SBMA, we will test the effect of neuropeptides that stimulates the generation of cAMP and activation of PKA, to target SBMA spinal cord.
EU contribution: EUR 178 760,7
VIA MOREGO 30