PUBLICATION
Lanthionine ketimine-5-ethyl ester provides neuroprotection in a zebrafish model of okadaic acid-induced Alzheimer's disease
- Authors
- Koehler, D., Shah, Z.A., Hensley, K., Williams, F.E.
- ID
- ZDB-PUB-180224-6
- Date
- 2018
- Source
- Neurochemistry international 115: 61-68 (Journal)
- Registered Authors
- Williams, Fred
- Keywords
- BDNF, CREB, Lanthionine ketimine-5-ethyl-ester, Okadaic acid, PKB/Akt, Zebrafish
- MeSH Terms
-
- Alzheimer Disease/chemically induced
- Alzheimer Disease/drug therapy*
- Amino Acids, Sulfur/pharmacology*
- Animals
- Brain/drug effects
- Brain/metabolism
- Cells, Cultured
- Female
- Male
- Mice
- Neuroprotection/drug effects*
- Neuroprotective Agents/pharmacology
- Okadaic Acid/pharmacology*
- Zebrafish
- PubMed
- 29475037 Full text @ Neurochem. Int.
Citation
Koehler, D., Shah, Z.A., Hensley, K., Williams, F.E. (2018) Lanthionine ketimine-5-ethyl ester provides neuroprotection in a zebrafish model of okadaic acid-induced Alzheimer's disease. Neurochemistry international. 115:61-68.
Abstract
Okadaic acid (OKA) is a protein phosphatase-2A inhibitor that is used to induce neurodegeneration and study disease states such as Alzheimer's disease (AD). Lanthionine ketimine-5-ethyl ester (LKE) is a bioavailable derivative of the naturally occurring brain sulfur metabolite, lanthionine ketimine (LK). In previously conducted studies, LKE exhibited neuroprotective and neurotrophic properties in murine models but its mechanism of action remains to be clarified. In this study, a recently established zebrafish OKA-induced AD model was utilized to further elucidate the neuroprotective and neurotrophic properties of LKE in the context of an AD-like condition. The fish were divided into 3 groups containing 8 fish per group. Group #1 = negative control, Group #2 = 100 nM OKA, Group #3 = 100 nM OKA +500 μM LKE. OKA caused severe cognitive impairments in the zebrafish, but concomitant treatment with LKE protected against cognitive impairments. Further, LKE significantly and substantially reduced the number of apoptotic brain cells, increased brain-derived neurotrophic factor (BDNF), and increased phospho-activation of the pro-survival factors pAkt (Ser 473) and pCREB (Ser133). These findings clarify the neuroprotective and neurotrophic effects of LKE by highlighting particular survival pathways that are bolstered by the experimental therapeutic LKE.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping