RESUMO
The identification and characterization of multipotent neural precursors open the possibility of transplant therapies, but this approach is complicated by the widespread pathology of many degenerative diseases. Activation of endogenous precursors that support regenerative mechanisms is a possible alternative. We have previously shown that Notch ligands promote stem cell survival in vitro. Here, we show that there is an intimate interaction between insulin and Notch receptor signaling. Notch ligands also expand stem cell numbers in vivo with correlated benefits in brain ischemia. We now show that insulin promotes recovery of injured dopamine neurons in the adult brain. This response suggests that activating survival mechanisms in neural stem cells will promote recovery from progressive degenerative disease.
Assuntos
Encefalopatias/metabolismo , Neurônios/metabolismo , Células-Tronco/metabolismo , Adulto , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Encefalopatias/tratamento farmacológico , Encefalopatias/patologia , Sobrevivência Celular/efeitos dos fármacos , Dopamina/metabolismo , Humanos , Insulina/metabolismo , Insulina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Ligantes , Proteínas de Membrana/metabolismo , Proteínas de Membrana/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oxidopamina/toxicidade , Coelhos , Ratos , Receptores Notch/metabolismo , Proteínas Repressoras , Transdução de Sinais , Células-Tronco/efeitos dos fármacos , Células-Tronco/patologiaRESUMO
In this prospective controlled study, a 30-g protein-restricted diet supplemented by keto acids resulted in a delayed rate of progression of chronic renal failure. The effect of this treatment differed according to the underlying renal disease. The rate of progression of chronic renal failure was delayed by a factor of at least 2. A need for long-term observations to quantify the effectiveness of this therapy is shown. A new pragmatic approach to the evaluation of long-term studies in patients with chronic renal failure is demonstrated.
