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Histidyl-Proline Di...
Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates
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- Turkez, Hasan (författare)
- Ataturk Univ, Dept Med Biol, Fac Med, TR-25240 Erzurum, Turkey.
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- Cacciatore, Ivana (författare)
- Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, CH, Italy.
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- Arslan, Mehmet Enes (författare)
- Erzurum Tech Univ, Dept Mol Biol & Genet, Fac Sci, TR-25050 Erzurum, Turkey.
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- Fornasari, Erika (författare)
- Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, CH, Italy.
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- Marinelli, Lisa (författare)
- Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, CH, Italy.
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- Di Stefano, Antonio (författare)
- Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, CH, Italy.
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- Mardinoglu, Adil (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
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Ataturk Univ, Dept Med Biol, Fac Med, TR-25240 Erzurum, Turkey Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, CH, Italy. (creator_code:org_t)
- 2020-05-09
- 2020
- Engelska.
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:5
- Relaterad länk:
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https://doi.org/10.3...
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https://www.mdpi.com...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer's disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 (A beta(1-42)) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), alpha- and beta-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2 '-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against A beta(1-42)-induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by A beta(1-42) exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- histidyl-proline diketopiperazine
- Alzheimer's disease
- amyloid-beta 1-42
- neuroprotection
- novel therapeutics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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