glycyl-prolyl-glutamic-acid and Alzheimer-Disease

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.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Apoptosis; Cell Death; Cell Differentiation; Cell Line, Tumor; Drug Design; Humans; Models, Biological; Necrosis; Neuroprotective Agents; Oligopeptides; Oxidation-Reduction; Peptidomimetics

This study investigated the anti-inflammatory effects of novel pseudotripeptides (GPE 1-3) as potential candidates to counteract neuroinflammation processes in Alzheimer's disease. GPE 1-3 pseudotripeptides are synthetic derivatives of Gly-l-Pro-l-Glu (GPE), the N-terminal tripeptide of IGF-1, obtained through the introduction of isosteres of the amidic bond (aminomethylene unit) to increase the metabolic stability of the native tripeptide. The results showed that all synthetic derivatives possessed higher half-lives (t

Topics: Alzheimer Disease; Cytokines; Dose-Response Relationship, Drug; Humans; Inflammation; Molecular Structure; Neuroprotective Agents; Oligopeptides; Structure-Activity Relationship; THP-1 Cells

In this study, effects of LA-GPE (R-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of Aβ

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Apoptosis; Cell Line, Tumor; Humans; L-Lactate Dehydrogenase; Mitochondria; Neuroprotective Agents; Oligopeptides; Oxidative Stress; Peptide Fragments