Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29614684
DOI
10.3233/jad-171041
PII: JAD171041
Knihovny.cz E-resources
- Keywords
- Alzheimer’s disease, THY-Tau22 mice, palm11-PrRP31, spatial memory, synaptic plasticity, tau hyperphosphorylation,
- MeSH
- Maze Learning drug effects physiology MeSH
- Phosphorylation drug effects MeSH
- Hippocampus drug effects metabolism pathology MeSH
- Prolactin-Releasing Hormone analogs & derivatives pharmacology therapeutic use MeSH
- Memory, Short-Term drug effects physiology MeSH
- Disease Models, Animal MeSH
- Mice, Transgenic MeSH
- Neuroprotective Agents pharmacology MeSH
- Memory Disorders drug therapy metabolism pathology MeSH
- Spatial Memory drug effects physiology MeSH
- tau Proteins metabolism MeSH
- Tauopathies drug therapy metabolism pathology psychology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Prolactin-Releasing Hormone MeSH
- Mapt protein, mouse MeSH Browser
- Neuroprotective Agents MeSH
- palm11-PrRP31 MeSH Browser
- tau Proteins MeSH
Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology. Seven-month-old THY-Tau22 mice were subcutaneously infused with palm11-PrRP31 for 2 months. Spatial memory was tested before and after the treatment, using a Y-maze. At the end of the treatment, mice were sacrificed by decapitation and hippocampi were dissected and analyzed by immunoblotting with specific antibodies. Treatment with palm11-PrRP31 resulted in significantly improved spatial memory. In the hippocampi of palm11-PrRP31-treated THY-Tau22 mice, tau protein phosphorylation was attenuated at Thr231, Ser396, and Ser404, the epitopes linked to AD progression. The mechanism of this attenuation remains unclear, since the activation of those kinases most implicated in tau hyperphosphorylation, such as GSK-3β, JNK, or MAPK/ERK1/2, remained unchanged by palm11-PrRP31 treatment. Furthermore, we observed a significant increase in the amount of postsynaptic density protein PSD95, and a non-significant increase of synaptophysin, both markers of increased synaptic plasticity, which could also result in improved spatial memory of THY-Tau22 mice treated with palm11-PrRP31. Palm11-PrRP31 seems to be a potential tool for the attenuation of neurodegenerative disorders in the brain. However, the exact mechanism of its action must be elucidated.
Institute of Organic Chemistry and Biochemistry AS CR Prague Czech Republic
Institute of Physiology AS CR Prague Czech Republic
University of Chemistry and Technology Prague Czech Republic
References provided by Crossref.org
An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis
Prolactin-Releasing Peptide: Physiological and Pharmacological Properties
