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The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes

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Abstract

Reelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer’s disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effects of α-boswellic acid (ABA) as one of the major component of Boswellia serrata resin on primary fetal human astrocytes under a stress paradigm as a possible model for AD through study on Reelin cascade. For this aim, we used streptozotocin (STZ), in which from an outlook generates Alzheimer’s hallmarks in astrocytes, and assayed Reelin expression, Tau and Akt phosphorylation as well as reactive oxygen species (ROS) generation and apoptosis in the presences of ABA. Our results indicated that while STZ (100 µM) down-regulated the expression of Reelin, ABA (25 µM) up-regulated its expression (p < 0.01) for 24 h. ABA efficiently reduced hyperphosphorylated Tau (Ser404) in STZ-treated astrocytes (p < 0.01). Furthermore, STZ-induced apoptosis by increasing cleaved caspase three (p < 0.01) and ROS generation (p < 0.01), a further pathological hallmark of Tauopathy. On the other hand, ABA decreased ROS generation and promoted proliferation of astrocytes through elevating Survivin expression (p < 0.01). These results showed that ABA could be considered as a potent therapeutic agent for prevention and decreasing the progression of Alzheimer’s hallmarks in astrocytes; however, more in vivo studies would be needed.

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Abbreviations

ABA:

α-Boswellic acid

BBA:

β-Boswellic acid

AD:

Alzheimer’s disease

STZ:

Streptozotocin

ROS:

Reactive oxygen species

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Acknowledgments

The authors appreciate the financial support of this investigation by the Research Council of University of Tehran. Meanwhile, the authors thank Prof. S. Hossein Fatemi (University of Minnesota), Mr. Nima Allahyari and Mr. Houman Norouzi for their kind assistance.

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  1. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

    Esmat Fathi, Fatemeh Hedayati Katouli, Gholam Hossein Riazi, Marzieh Dehghan Shasaltaneh, Elham Parandavar, Samaneh Bayati, Ali Afrasiabi & Reza Nazari

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  1. Esmat Fathi
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Fathi, E., Katouli, F.H., Riazi, G.H. et al. The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes. Neuromol Med 19, 136–146 (2017). https://doi.org/10.1007/s12017-016-8437-3

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