Efecto antiapoptotico del PF 9601N y derivados en neuroblastomas humanos tipo SH-SY5Y tratados con MPP+ como modelo de toxicidad dopaminérgica: implicaciones terapeúticas en la enfermedad de Parkinson

  • Unzeta Lopez, Mercedes (Principal Investigator)
  • Hernández Guillamón, Maria Mar (Scholar)
  • Pasto Vilardell, Manuel (Investigator)

Project Details

Description

Parkinson's disease is a progressive neurodegenerative disorder that could be induced by a desregulation of the apoptotic process in the striatum. The PF 9601N [N-(2-propynyl)-2-(5-benzyloxy -indolyl) methylamie] and analogues are a novel series of molecules non-amphetamine type, that have shown a neuroprotective effect "in vitro" as well as "in vivo" using MPTP as dopaminergic toxin in C57/bl mice, as experimental model of Parkinsoniusm. Preliminary results have shown that these compounds stimulates the expression of the antiapoptótic protein Bcl2 and can block the opening of the mitochondrial pore. Thus the aims of this project will be 1st to determine the antipoptotic effect of PF 9601N and derivatives in human neuroblastoma SHSY5Y type cells, inducing apoptosis with MPP+. 2nd We will study the involvement of mitochondrial pathway in the anti-apoptotic effect observed before, determining the effect of PF 9601 N and analogues on the expression of the Bcl-2 protein as well as the effect on the mitochondrial opening pore and the mitochondrial membrane potential. 3rrd The structural-activity realationship studies we will allow to determine the structural features responsible of the antiapoptótic effect, and to design new molecules able to delay the progressive neurodegeneration in Parkinson´s disease
StatusFinished
Effective start/end date15/12/0314/12/06

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