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Article

Glycyl-L-Prolyl-L-Glutamate Pseudotripeptides for Treatment of Alzheimer’s Disease

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Department of Medical Biology, Faculty of Medicine, Atatürk University, 25240 Erzurum, Turkey
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Department of Pharmacy, Univerisity “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo, Chieti, Italy
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Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, 25200 Erzurum, Turkey
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Department of Internal Medicine, Erzurum Regional Training and Research Hospital, Health Sciences University, 25200 Erzurum, Turkey
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Department of Medical Genetics, Faculty of Medicine, Atatürk University, 25240 Erzurum, Turkey
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Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, 25240 Erzurum, Turkey
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Science for Life Laboratory, KTH—Royal Institute of Technology, 24075 Stockholm, Sweden
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Centre for Host-Microbiome Interactions, Dental Institute, King’s College London, London SE1 9RT, UK
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Authors to whom correspondence should be addressed.
Biomolecules 2021, 11(1), 126; https://doi.org/10.3390/biom11010126
Received: 10 December 2020 / Revised: 13 January 2021 / Accepted: 15 January 2021 / Published: 19 January 2021
So far, there is no effective disease-modifying therapies for Alzheimer’s Disease (AD) in clinical practice. In this context, glycine-L-proline-L-glutamate (GPE) and its analogs may open the way for developing a novel molecule for treating neurodegenerative disorders, including AD. In turn, this study was aimed to investigate the neuroprotective potentials exerted by three novel GPE peptidomimetics (GPE1, GPE2, and GPE3) using an in vitro AD model. Anti-Alzheimer potentials were determined using a wide array of techniques, such as measurements of mitochondrial viability (MTT) and lactate dehydrogenase (LDH) release assays, determination of acetylcholinesterase (AChE), α-secretase and β-secretase activities, comparisons of total antioxidant capacity (TAC) and total oxidative status (TOS) levels, flow cytometric and microscopic detection of apoptotic and necrotic neuronal death, and investigating gene expression responses via PCR arrays involving 64 critical genes related to 10 different pathways. Our analysis showed that GPE peptidomimetics modulate oxidative stress, ACh depletion, α-secretase inactivation, apoptotic, and necrotic cell death. In vitro results suggested that treatments with novel GPE analogs might be promising therapeutic agents for treatment and/or or prevention of AD. View Full-Text
Keywords: Alzheimer’s disease; neurotoxicity; glycine-proline-glutamate peptidomimetics; in vitro cell culture model; gene expressions Alzheimer’s disease; neurotoxicity; glycine-proline-glutamate peptidomimetics; in vitro cell culture model; gene expressions
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MDPI and ACS Style

Turkez, H.; Cacciatore, I.; Marinelli, L.; Fornasari, E.; Aslan, M.E.; Cadirci, K.; Kahraman, C.Y.; Caglar, O.; Tatar, A.; Di Biase, G.; Hacimuftuoglu, A.; Di Stefano, A.; Mardinoglu, A. Glycyl-L-Prolyl-L-Glutamate Pseudotripeptides for Treatment of Alzheimer’s Disease. Biomolecules 2021, 11, 126. https://doi.org/10.3390/biom11010126

AMA Style

Turkez H, Cacciatore I, Marinelli L, Fornasari E, Aslan ME, Cadirci K, Kahraman CY, Caglar O, Tatar A, Di Biase G, Hacimuftuoglu A, Di Stefano A, Mardinoglu A. Glycyl-L-Prolyl-L-Glutamate Pseudotripeptides for Treatment of Alzheimer’s Disease. Biomolecules. 2021; 11(1):126. https://doi.org/10.3390/biom11010126

Chicago/Turabian Style

Turkez, Hasan, Ivana Cacciatore, Lisa Marinelli, Erika Fornasari, Mehmet Enes Aslan, Kenan Cadirci, Cigdem Yuce Kahraman, Ozge Caglar, Abdulgani Tatar, Giuseppe Di Biase, Ahmet Hacimuftuoglu, Antonio Di Stefano, and Adil Mardinoglu. 2021. "Glycyl-L-Prolyl-L-Glutamate Pseudotripeptides for Treatment of Alzheimer’s Disease" Biomolecules 11, no. 1: 126. https://doi.org/10.3390/biom11010126

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