Asunto(s)
Osteoporosis/epidemiología , Adulto , Anciano , Instituciones de Atención Ambulatoria , Femenino , Humanos , Medicina Interna , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Prevalencia , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiologíaRESUMEN
The pro-form of nerve growth factor (pro-NGF) has been shown to be a high affinity ligand for p75NTR and to induce apoptosis through this receptor. It has been reported that pro-NGF, rather than mature NGF, is the predominant form of this neurotrophin in human brain. In the present work we studied the potential involvement of pro-NGF purified from human brains affected by Alzheimer's disease (AD), where it is especially abundant, in the neuronal apoptosis observed in this disease. Western blot analysis of human brain tissue showed the existence of several pro-NGF forms. Some of these pro-NGF forms were significantly increased in AD brain cortex in a disease stage-dependent manner. Pro-NGF, purified by chromatography from human AD brains, induced apoptotic cell death in sympathetic neurons and in a p75NTR stably transfected cell line. Blocking p75NTR in cell culture abolished neuronal apoptosis caused by pro-NGF. p75NTR-transfected cells underwent apoptosis in the presence of pro-NGF while control wild-type cells did not. Taken together, these results indicate that pro-NGF purified from AD human brains can induce apoptosis in neuronal cell cultures through its interaction with the p75NTR receptor.
Asunto(s)
Apoptosis , Factor de Crecimiento Nervioso/biosíntesis , Factor de Crecimiento Nervioso/fisiología , Neuronas/patología , Precursores de Proteínas/biosíntesis , Precursores de Proteínas/fisiología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Células 3T3 , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Western Blotting , Encéfalo/metabolismo , Encéfalo/patología , Células Cultivadas , Cromatografía , Densitometría , Femenino , Humanos , Inmunohistoquímica , Masculino , Ratones , Persona de Mediana Edad , Factores de Crecimiento Nervioso/metabolismo , Células PC12 , Ratas , Ratas Sprague-Dawley , Receptor de Factor de Crecimiento Nervioso , Factores de Tiempo , Transfección , Tripsina/farmacologíaRESUMEN
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