RESUMO
beta-amyloid levels are elevated in Down syndrome (DS) patients throughout life and are believed to cause Alzheimer's disease (AD) in adult members of this population. However, it is not known if beta-amyloid contributes to intellectual disability in younger individuals. We used a gamma-secretase inhibitor to lower beta-amyloid levels in young mice that model DS. This treatment corrected learning deficits characteristic of these mice, suggesting that beta-amyloid-lowering therapies might improve cognitive function in young DS patients.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Síndrome de Down/metabolismo , Aprendizagem , Memória , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Inibidores Enzimáticos/farmacologia , Camundongos , Camundongos TransgênicosRESUMO
Substituents on the pyridinium ring of N-methylpyridinium derivatives, especially those on the 2- or 4-positions, have a large effect on the (1)H and (13)C NMR chemical shifts of the N-methyl group. Reasonable correlations between the chemical shift changes and the resonance substituent constants are observed. The dual substituent parameter approach provides an excellent correlation when a combination of polar and resonance substituent constants is employed.