LORENZO ALFREDO GUILLERMO
Congresos y reuniones científicas
Título:
African-Mandenka APP mutant protects from neurodegeneration in Alzheimer´s disease model
Autor/es:
BIGNANTE, ELENA ANAHI; FLORENCIA HEREDIA; ZAMPONI EMILIANO; PINOTTI JUAN DIEGO; HELGUERA PABLO; ALFREDO LORENZO
Lugar:
Puerto Varas
Reunión:
Congreso; XXVII Chilean Society for Cell Biology; 2013
Institución organizadora:
Soc Biol Cel Chile
Resumen:
Aggregation anddeposition of β-Amyloid(Aβ)is associated with neurodegeneration and Alzheimer disease (AD). Aβ is generated by proteolysis of the AmyloidPrecursor Protein (APP), a transmembrane protein with a receptor-likestructure. App mutations that affectAβgeneration or predispose to its aggregation are pathogenic and conduce toearly-onset genetic forms of AD. APP is also a molecular target for toxic Aβ-assemblies mediating neurodegeneration throughactivation of heterotrimeric Go protein. The histidine doublet at positions657-658 on APP are critical for Go activation. Recently, a new mutation on App was found in a neurologicallyhealthy individual from the African-Mandenka ethnic. The mutation promotes thesubstitution of a histidine 658 by a proline (APPH658P) and is considered notpathogenic, although it had not been experimentally analyzed. Here wecharacterized APPH658P mutant in cellular models. We found that the mutationdoes not affect APP processing, or its ability to interact with toxic Aβaggregates. Significantly, APPH658P is unable to promote Aβ-neurodegenerationin primary hippocampal neurons. Moreover, APPH658P acts as a dominant-negativethat prevents Aβ-induced toxicity that depends on activation of Go by APPwt.Our data suggest that the Mandenka APP mutant could protect fromAD-neurodegeneration to its carriers.
