Abstract

Dopamine neuron stimulating peptide‐11 (DNSP‐11), an eleven amino acid amidated peptide derived from the glial cell‐line derived neurotrophic factor (GDNF) prosequence, has been shown recently to provide neuroprotective and neurorestorative effects in dopaminergic cell culture and parkinsonian rat model systems. However, unlike GDNF, DNSP‐11 was found to prevent staurosporine‐induced toxicity and cytochrome c release from mitochondria in nutrient‐deprived dopaminergic B65 cells. The objective of this study is to investigate the neuroprotective effects of DNSP‐11 on the mitochondria. We treated dopaminergic cell lines with mitochondrial‐specific toxins and evaluated DNSP‐11’s protective effects by measuring mitochondrial potential, caspase‐3 activity, and TUNEL staining assays. In addition, proteomic profile analyses were performed to determine changes in the membrane, cytosolic and mitochondrial proteins involved in DNSP‐11 protection. These data support a mitochondrial neuroprotective hypothesis and further suggest that DNSP‐11 is a promising candidate for further evaluation as a downstream therapeutic for age‐related neurogenerative diseases, like Parkinson's disease. Support provided by: NIH COBRE Pilot (P20RR20171), NIA (T32 AG000242), NIDA (T32 DA022738), NINDS (NS039787), PhRMA Foundation, and University of Kentucky College of Medicine Start‐up Funds.

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