Prosaptide™ D5, a retro-inverso 11-mer peptidomimetic, rescued dopaminergic neurons in a model of Parkinson’s disease

SPECIFIC AIMSOur aim was to evaluate the efficacy of ProsaptideTM D5, a bioactive protease-resistant 11-mer retro-inverso trophic peptidomimetic of prosaposion, in a model of Parkinson’s disease (PD). Experiments were devised to test the efficacy of ProsaptideTM D5 both in vitro and in vivo in the rescue of dopaminergic (DA) neurons from MPP+/MPTP toxicity, a specific toxin for DA neurons.PRINCIPAL FINDINGS1. ProsaptideTM D5 promoted neurite outgrowth and rescued DA neuron from MPP+ toxicity in the primary culture of DA neuronsThe addition of MPP+ (48 h incubation at 20 μM) significantly inhibited neurite outgrowth of primary DA neurons; after addition of MPP+, the average number of neurites per neuron decreased to 55% (primary neurites) and 34% (secondary neurites) of controls, respectively, and the neurites were also shorter in length (Fig. 1B⤻ ). ProsaptideTM D5 treatment (1 ng/ml) promoted neurite outgrowth in the presence of MPP+ (Fig. 1C⤻ , D⤻ ); the numbers of both primary and secondary neurites we...