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| Author(s): |
Evandro Pizeta Semighini
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2013-06-13 |
| Examining board members: |
Carlos Henrique Tomich de Paula da Silva;
Fernando Batista da Costa;
Laurent Emmanuel Dardenne;
Flavio da Silva Emery;
Carlos Alberto Montanari
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| Advisor: | Carlos Henrique Tomich de Paula da Silva |
| Abstract | |
The Alzheimer\'s disease is the major cause of elderly dementia: it affects 10% of global population with 65 years old and about 50% of individuals with 85 years old or more. The evolution of the disease symptoms is associated with structural changes in cholinergic synapses at certain brain regions. The major pathophysiological feature of AD is the deposition of extracellular neuritic plaques in areas of the brain related to memory. The ?-amyloid peptide 40/42 constitutes the plaques. It\'s formed by cleavage of the amyloid precursor protein during its metabolism by the amyloidogenic pathway, which starts with the ?-secretase enzyme. The goal of this project was the planning and evaluation of new ?-secretase inhibitors activity. For this, we used different molecular modeling and drug design techniques, based on the ?-secretase inhibitors described in the literature, whose structures are deposited in the PDB, with subsequent in vitro evaluation of this molecules activity. The in vitro assays showed three molecules able to inhibit ?-secretase at 1 µM. (AU) | |
| FAPESP's process: | 08/10805-8 - Rational design of beta-secretase inhibitors in Alzheimer's Disease |
| Grantee: | Evandro Pizeta Semighini |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |