Objectives: Alzheimer\\\\\\\\\\\\\\\'s disease (AD) is a progressive neurodegenerative disorder involving misfolding and aggregation of a fibrillar 42aa form of β-amyloid (A β 1–42) peptide, which triggers a cellular stress response called the unfolded protein response (UPR). UPR accompanies the activation of protective cascades such as PERK pathway. Recent studies have demonstrated that PERK pathway transmits a stress signal that arrests the cell cycle in G1. Cyclin D1 is a regulator of G1 to S phase transition of cell cycle. This study was conducted to evaluate the expression of cyclin D1 mRNA in mice after induction of Alzheimer’s disease. Materials & Methods: Bilateral infusions of 1mM fibrillar Aβ 1–42 (n=14) or PBS (for control littermates, n=12) were made stereotaxically into the dorsal hippocampus, using31-gauage cannulae connected by PE tubing to5-µl Hamilton syringes mounted on a Hamilton syringe drive. Two weeks later, total RNA from mouse brain tissues were prepared using Trizol according to the manufacturer’s guidelines, from which one microgram was used for cDNA synthesis and PCR. Semiquantitative analysis using the cyclin D1 primers was performed by monitoring in real time the increase in fluorescence of SYBR Green dye and normalized against the GAPDH expression levels. Results & Conclusion: The real-time RT-PCR analysis revealed a significant decrease in cyclin D1 mRNA levels in Aβ 1–42 implanted mouse brain compared with control littermates. This might have an impact on neuronal death and other pathological aspects of AD. Glycogen synthase kinase-3 β (GSK-3β) is a cytoplasmic protein kinase that is activated by PERK pathway and is capable of regulating cyclin D1 expression. Therefore pharmacological inhibitors of GSK-3 β such as thiadiazolidinone compound might be of beneficial to increase the expression of cyclin D1 and be a good strategy for the treatment of AD. Keywords: Cyclin D1, Alzheimer’s disease, Real time RT-PCR

Keywords