(943.6) DNSP-11 reduces 6-OHDA-induced caspase 3/7 activation in an SH-SY5Y cell model: Potential Role of ERK signaling pathway?

Poster Board Number: B199

Mayur Parmar (Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University), Erika Allen (Lake Erie College of Osteopathic Medicine), Shreya Narain (Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University), Deepesh Khanna (Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University), Jane Cavanaugh (School of Pharmacy, Duquesne University)

Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a promising therapeutic molecule for treating Parkinson’s disease (PD). However, because of the failure of GDNF infusion in clinical trials, due to its poor bio-distribution, there was a need to develop other molecules with similar properties to GDNF that have improved bioavailability and administration. Dopamine neuron stimulating peptide-11 (DNSP-11) is a synthetic, amidated 11-amino acid neuroactive peptide derived from the human proGDNF domain. DNSP-11 has been shown to protect dopaminergic cells in vitro and restore dopaminergic activity in vivo. Therefore, the objective of our study was to test if DNSP-11 protects human dopaminergic neuroblastoma SH-SY5Y cells against 6-OHDA induced toxicity and to elucidate the protective mechanism of action. DNSP-11 reduced the 6-OHDA–induced increase in caspase-3/7 activity in SH-SY5Y cells at early time points, indicating possible protection against apoptosis. DNSP-11 also activated the cell survival signaling pathways, ERK1, 2, and 5 in SH-SY5Y cells. In addition, a single injection of DNSP-11 in adult rat striatum leads to modulation of these ERK proteins in the substantia nigra. Overall, the results indicate that DNSP-11 protects human dopaminergic neuroblastoma cells against apoptotic cell death and activates neuroprotective ERK signaling pathways, suggesting its potential therapeutic role in Parkinson’s disease (PD).