Artículo
Inhibition of RhoA GTPase and the subsequent activation of PTP1B protects cultured hippocampal neurons against amyloid b toxicity
Autor/es | Chacón Fernández, Pedro José
García Mejías, Rosa Rodríguez Tebar, Alfredo |
Fecha de publicación | 2011 |
Fecha de depósito | 2017-09-14 |
Publicado en |
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Resumen | Background: Amyloid beta (Ab) is the main agent responsible for the advent and progression of Alzheimer’s
disease. This peptide can at least partially antagonize nerve growth factor (NGF) signalling in neurons, which ... Background: Amyloid beta (Ab) is the main agent responsible for the advent and progression of Alzheimer’s disease. This peptide can at least partially antagonize nerve growth factor (NGF) signalling in neurons, which may be responsible for some of the effects produced by Ab. Accordingly, better understanding the NGF signalling pathway may provide clues as to how to protect neurons from the toxic effects of Ab. Results: We show here that Ab activates the RhoA GTPase by binding to p75NTR, thereby preventing the NGFinduced activation of protein tyrosine phosphatase 1B (PTP1B) that is required for neuron survival. We also show that the inactivation of RhoA GTPase and the activation of PTP1B protect cultured hippocampal neurons against the noxious effects of Ab. Indeed, either pharmacological inhibition of RhoA with C3 ADP ribosyl transferase or the transfection of cultured neurons with a dominant negative form of RhoA protects cultured hippocampal neurons from the effects of Ab. In addition, over-expression of PTP1B also prevents the deleterious effects of Ab on cultured hippocampal neurons. Conclusion: Our findings indicate that potentiating the activity of NGF at the level of RhoA inactivation and PTP1B activation may represent a new means to combat the noxious effects of Ab in Alzheimer’s disease. |
Agencias financiadoras | Ministerio de Educación y Ciencia (MEC). España |
Identificador del proyecto | BFU2005-05629 |
Cita | Chacón Fernández, P.J., García Mejías, R. y Rodríguez Tebar, A. (2011). Inhibition of RhoA GTPase and the subsequent activation of PTP1B protects cultured hippocampal neurons against amyloid b toxicity. Molecular Neurodegeneration, 6 (14), 1-11. |
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