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A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells

[ Vol. 14 , Issue. 12 ]

Author(s):

Sourav Kumar, Ashim Paul, Sourav Kalita, Awanish Kumar, Saurabh Srivastav, Somoday Hazra, Anup Kumar Ghosh, Bhubaneswar Mandal and Amal Chandra Mondal*   Pages 1293 - 1304 ( 12 )

Abstract:


Background: Alzheimer's disease (AD), a common protein misfolding progressive neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) protein accumulate 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 of AD 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 assessed 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 ameliorated Aβ1-40 induced neurotoxicity and attenuates ROS generation that mediates 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.

Keywords:

Alzheimer's disease, amyloid-β, apoptosis, pro-drug peptide, reactive oxygen species, SH-SY5Y cells.

Affiliation:

Department of Physiology, Neuroscience Research Unit, RPM College, Uttarpara, Hooghly, WB-712258, Department of Chemistry, Indian Institute of Technology Guwahati (IITG), North Guwahati, Assam-781039, Department of Chemistry, Indian Institute of Technology Guwahati (IITG), North Guwahati, Assam-781039, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110 067, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110 067, Department of Physiology, Neuroscience Research Unit, RPM College, Uttarpara, Hooghly, WB-712258, Department of Instrumentation Science, Jadavpur University, Kolkata, West Bengal-700032, Department of Chemistry, Indian Institute of Technology Guwahati (IITG), North Guwahati, Assam-781039, School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi-110 067



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