title: The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes.
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.
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Esmat
authors: E
authors: Fathi
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Fatemeh Hedayati
authors: FH
authors: Katouli
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. ghriazi@ut.ac.ir.
authors: Gholam Hossein
authors: GH
authors: Riazi
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Marzieh Dehghan
authors: MD
authors: Shasaltaneh
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Elham
authors: E
authors: Parandavar
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Samaneh
authors: S
authors: Bayati
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Ali
authors: A
authors: Afrasiabi
authors: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors: Reza
authors: R
authors: Nazari
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D013311:Streptozocin / Q000494:pharmacology; D000077022:Survivin; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D051034:Inhibitor of Apoptosis Proteins; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D000091042:Reelin Protein; D000077022:Survivin; D016875:tau Proteins; D010768:Phosphoserine; D013311:Streptozocin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: Alpha boswellic acid; Alzheimer’s disease; Astrocytes; Reelin; Streptozotocin; Tau