Glycyl-L-prolyl-L-glutamate pseudotripeptides for treatment of Alzheimer’s disease

Hasan Turkez; 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; Adil Mardinoglu

doi:10.3390/biom11010126

Glycyl-L-prolyl-L-glutamate pseudotripeptides for treatment of Alzheimer’s disease

Hasan Turkez^*, 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, Adil Mardinoglu

^*Corresponding author for this work

Centre for Host Microbiome Interactions

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

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.

Original language	English
Article number	126
Pages (from-to)	1-17
Number of pages	17
Journal	Biomolecules
Volume	11
Issue number	1
DOIs	https://doi.org/10.3390/biom11010126
Publication status	Published - Jan 2021

Keywords

Alzheimer’s disease
Gene expressions
Glycine-proline-glutamate peptidomimetics
In vitro cell culture model
Neurotoxicity

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10.3390/biom11010126

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title = "Glycyl-L-prolyl-L-glutamate pseudotripeptides for treatment of Alzheimer{\textquoteright}s disease",

abstract = "So far, there is no effective disease-modifying therapies for Alzheimer{\textquoteright}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.",

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AU - Cacciatore, Ivana

AU - Marinelli, Lisa

AU - Fornasari, Erika

AU - Aslan, Mehmet Enes

AU - Cadirci, Kenan

AU - Kahraman, Cigdem Yuce

AU - Caglar, Ozge

AU - Tatar, Abdulgani

AU - Di Biase, Giuseppe

AU - Hacimuftuoglu, Ahmet

AU - Di Stefano, Antonio

AU - Mardinoglu, Adil

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AB - 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.

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Glycyl-L-prolyl-L-glutamate pseudotripeptides for treatment of Alzheimer’s disease

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Keywords

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