Autophagy-dependent mechanism of genistein-mediated elimination of behavioral and biochemical defects in the rat model of sporadic Alzheimer's disease.
PBN-AR
Instytucja
Instytut Biochemii i Biofizyki Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
EN
Czasopismo
NEUROPHARMACOLOGY
ISSN
0028-3908
EISSN
Wydawca
PERGAMON-ELSEVIER SCIENCE LTD
DOI
URL
Rok publikacji
2019
Numer zeszytu
brak
Strony od-do
332-346
Numer tomu
148
Liczba arkuszy
Słowa kluczowe
EN
Alzheimer's disease;
Autophagy;
Correction of behavior;
Genistein;
Hyperphosphorylated tau protein;
Rat model;
Streptozotocinβ-amyloid
Streszczenia
Język
EN
Treść
Alzheimer's disease is one of severe neurological diseases for which no effective treatment is currently available. The use of genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) has been proposed previously as one of approaches to improve the disease symptoms, as some positive effects of this compound in cellular and animal models were reported. Inhibition of apoptosis and antioxidative functions were suggested as causes of these effects. Here, we demonstrate that high genistein dose (150 mg/kg/day; the dose significantly higher than those used previously in AD studies by others) can activate autophagy in the streptozotocin-induced rat model of the sporadic form of AD. We found that this dose of genistein led to complete degradation of β-amyloid and hyperphosphorylated tau protein in the brain, while experiments with cell cultures demonstrated that these effects require autophagy stimulation, which has never been shown before. Importantly, behavior of high dose genistein-treated AD rats was completely corrected, i.e. it was indistinguishable from that of healthy animals. This was observed in all performed behavioral tests: Morris water maze test, elevated plus-maze test, open field test, and locomotor measurements in an actometer. We conclude that autophagy-dependent mechanism is responsible for genistein-mediated correction of AD when this isoflavone is used at the high dose.
Inne
System-identifier
PX-5c751e16d5de6669ee00c682
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