A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in in vitro SH-SY5Y cells.

Background: Alzheimer’s disease (AD), a common protein misfolding neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) proteins accumulated into interneuronal spaces and plays a crucial role in the disease progression and its pathology. The aggregated Aβ exerts its neurotoxic effects by inducing apoptosis and oxidative damage in neuronal cells. Objectives: We have investigated the effects of a synthesized Pro-Drug peptide (PDp) on Aβ1-40 induced cytotoxicity in human neuroblastoma SH-SY5Y cells, represents one of the most effective strategies in combating human AD. Methods: Cells were treated with Aβ1–40 to induce cytotoxicity in the experimental model to screen the inhibitory effect of PDp. Assays for cell viability, reactive oxygen species (ROS) generation, levels of intracellular free Ca2+ and expression of key apoptotic proteins were performed by Western Blotting. Results: Our results showed that Aβ1–40 induces for 24h caused reduce cell viability, imbalance in Ca2+ homeostasis and increase in neuronal apoptosis in vitro. Treatment with PDp could effectively ameliorate Aβ1-40 induced neurotoxicity and attenuate ROS generation that mediate apoptotic signaling through Bcl-2, Bax, Caspase-3 activity and cytochrome C in the cells. Conclusion: These findings suggested that PDp has potential role as a neuroprotective and therapeutic agent for combating human AD.