Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesclinical medicineoncologyprostate cancer
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicineneurologyparkinson
- medical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis
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Call for proposal
FP7-PEOPLE-2011-IOF
See other projects for this call
Funding Scheme
MC-IOF - International Outgoing Fellowships (IOF)Coordinator
16163 Genova
Italy