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Abstract Title:

Ginkgo biloba extract (Egb761) attenuates zinc-induced tau phosphorylation at Ser262 by regulating GSK3β activity in rat primary cortical neurons.

Abstract Source:

Food Funct. 2015 Jun 2. Epub 2015 Jun 2. PMID: 26032477

Abstract Author(s):

Kyoung Ja Kwon, Eun Joo Lee, Kyu Suk Cho, Du-Hyong Cho, Chan Young Shin, Seol-Heui Han

Article Affiliation:

Kyoung Ja Kwon

Abstract:

In the brain, an excessive amount of zinc promotes the deposition ofβ-amyloid proteins and the intraneuronal accumulation of neurofibrillary tangles composed of hyperphosphorylated tau proteins. These consequences are key neuropathological traits that reflect Alzheimer's disease. Egb761, a standardized Ginkgo biloba extract, is a powerful antioxidant known to exhibit neuroprotective actions. In this study, we investigated whether Egb761 can counteract the zinc-induced tau phosphorylation in rat primary cortical neurons. To determine the modification of tau phosphorylation by Egb761 treatment, we conducted Western blot analyses, MTT assay, ROS measurements andimmunocytochemistry. We found that zinc-induced tau phosphorylation occurred at Ser262 in a time- and dose-dependent manner while other tau sites were not phosphorylated. Tau phosphorylation at Ser262 was increased 30 min after zinc treatment and peaked 3 h after zinc treatment (control: 100 ± 1.2%, 30 min: 253 ± 2.24%, 3 h: 373 ± 1.3%). Interestingly, Egb761 treatment attenuated the zinc-induced tau hyperphosphorylation at Ser262 in a concentration-dependent manner while the antioxidant N-acetylcysteine showed a similar effect. Furthermore, Egb761 prevented the zinc-induced activation ofp38 MAPK and GSK3β, as well as the zinc-induced increase in ROS production and neuronal cell death. Lithium chloride also inhibited the zinc-induced tau phosphorylation but did not affect ROS levels. These results suggest the potential of Egb761 for inhibiting the zinc-induced tau phosphorylation at Ser262 through its anti-oxidative actions involving the regulation of GSK3β. Therefore, Egb761 may be a candidate for the treatment of tauopathy present in neurological disorders such as Alzheimer's disease.

Study Type : In Vitro Study

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Sayer Ji
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