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A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells.
Curr Alzheimer Res. 2017; 14(12):1293-1304.CA

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.

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Authors+Show Affiliations

Kumar S
Department of Physiology, Neuroscience Research Unit, RPM College, Uttarpara, Hooghly, WB-712258. India.
Paul A
Department of Chemistry, Indian Institute of Technology Guwahati (IITG), North Guwahati, Assam-781039. India.
Kalita S
Department of Chemistry, Indian Institute of Technology Guwahati (IITG), North Guwahati, Assam-781039. India.
Kumar A
School of Life Sciences, Jawaharlal Nehru University, New Delhi-110 067. India.
Srivastav S
School of Life Sciences, Jawaharlal Nehru University, New Delhi-110 067. India.
Hazra S
Department of Physiology, Neuroscience Research Unit, RPM College, Uttarpara, Hooghly, WB-712258. India.
Ghosh AK
Department of Instrumentation Science, Jadavpur University, Kolkata, West Bengal-700032. India.
Mandal B
Department of Chemistry, Indian Institute of Technology Guwahati (IITG), North Guwahati, Assam-781039. India.
Mondal AC
School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi-110 067. India.

MeSH

Amyloid beta-PeptidesAnalysis of VarianceApoptosisCalciumCaspase 3Cell Line, TumorCell SurvivalCytochromes cHumansIntracellular FluidL-Lactate DehydrogenaseNeuroblastomaNeuronsPeptide FragmentsProto-Oncogene Proteins c-bcl-2Reactive Oxygen SpeciesSignal Transductionbcl-2-Associated X Protein

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28714389

Citation

Kumar, Sourav, et al. "A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in in Vitro SH-SY5Y Cells." Current Alzheimer Research, vol. 14, no. 12, 2017, pp. 1293-1304.
Kumar S, Paul A, Kalita S, et al. A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells. Curr Alzheimer Res. 2017;14(12):1293-1304.
Kumar, S., Paul, A., Kalita, S., Kumar, A., Srivastav, S., Hazra, S., Ghosh, A. K., Mandal, B., & Mondal, A. C. (2017). A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells. Current Alzheimer Research, 14(12), 1293-1304. https://doi.org/10.2174/1567205014666170713153414
Kumar S, et al. A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in in Vitro SH-SY5Y Cells. Curr Alzheimer Res. 2017;14(12):1293-1304. PubMed PMID: 28714389.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells. AU - Kumar,Sourav, AU - Paul,Ashim, AU - Kalita,Sourav, AU - Kumar,Awanish, AU - Srivastav,Saurabh, AU - Hazra,Somoday, AU - Ghosh,Anup Kumar, AU - Mandal,Bhubaneswar, AU - Mondal,Amal Chandra, PY - 2017/03/07/received PY - 2017/04/13/revised PY - 2017/06/29/accepted PY - 2017/7/18/pubmed PY - 2018/6/22/medline PY - 2017/7/18/entrez KW - Alzheimer's disease KW - SH-SY5Y cells. KW - amyloid-β KW - apoptosis KW - pro-drug peptide KW - reactive oxygen species SP - 1293 EP - 1304 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 14 IS - 12 N2 - 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. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/28714389/A_Peptide_Based_Pro_Drug_Ameliorates_Amyloid_β_Induced_Neuronal_Apoptosis_in_In_Vitro_SH_SY5Y_Cells_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1567-2050&volume=14&issue=12&spage=1293&aulast=Kumar DB - PRIME DP - Unbound Medicine ER -