Pharmacology of the intracellular pathways activated by amyloid beta protein.
Alzheimer's disease (AD) is a late-life cognitive disorder associated, among other things, to the presence of extracellular aggregates of fibrillar amyloid beta protein (Abeta). However, there is growing evidence that early stages of AD may be due to neuronal network dysfunction produced by the actions of soluble forms of Abeta. Therefore, the development of new therapeutic strategies to treat AD, at least during its first stages, may be focused on preventing or reversing, the deleterious effects that soluble Abeta exerts on neuronal circuit function. In order to do so, it is necessary to elucidate the pathophysiological processes involved in Abeta-induced neuronal network dysfunction and the molecular processes underlying such dysfunction. Over the last decades, there has been extensive research about the molecular mechanisms involved in the effects of Abeta as well as possible neuroprotective strategies against such effects. Here we are going to review some of the intracellular pathways triggered by Abeta, which involve membrane receptors such as nicotinic-R, NMDA-R, integrins, TNF-R1, RAGE, FPRL and p75NTR and their intracellular mediators such as GSK3, PKC, PI3K, Akt, FAK, MAPK family, Src family and cdk5. Several of these pathways may constitute therapeutic targets for the treatment of the Abeta-induced neuronal network dysfunction which is, at least in part, the basis for cognitive dysfunction in AD.
Balleza-Tapia
Hugo
H
Departamento de Farmacobiología, Cinvestav-Sede Sur, Col. Granjas Coapa, 14330, México, México.
Peña
Fernando
F
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D011956:Receptors, Cell Surface