REVERSAL OF MITOCHONDRIAL DAMAGE IN A RAT MODEL OF PARKINSONS-DISEASEBY A NEUROTROPHIC PEPTIDE (MPF ANALOG)

WE have previously shown that a metabolically stable analogue of MPF, the C-terminal tetrapeptide of human beta-endorphin of structure Lys-L ys-Gly-Glu, reduces the turning behaviour of rats with unilateral lesi ons of their nigro-striatal pathways. Transmission electron microscopy (TEM) has now revealed that this effect is related to reversal of the mitochondrial damage to substantia nigra (SN) neurones induced by the lesion. The results are consistent with the concept that an inherited defect in components of the mitochondrial enzyme system is the initia l step in the genesis of Parkinson's disease (PD). They also, in conju nction with known neurotropic properties of MPF, and our unpublished f inding of high concentrations of an MPF-like peptide in human basal ga nglia, suggest that MPF may have physiological significance in the dev elopment and regeneration of the human CNS.