EFFECT OF HYDROXYPROPYL-ß-CYCLODEXTRIN (HP-ß-CD) AND HP-ß-CD LOADED POLYMERIC NASAL MICROSPHERES ON THE EXPRESSIONS OF SOME mGluR5 AND CREB mRNAs IN EXPERIMENTAL MODEL OF ALZHEIMER’S DISEASE INDUCED BY AMYLOID-ß PEPTIDE (1-42)
Project no. 290 · Status: Kapanmış · 2018
Summary
The presence of amyloid ß (Aß) plaques is one of the key events for the neuropathogenesis of Alzheimer disease (AD). Aß peptide is natively unfolded yet conformationally plastic and prone to aggregation. In response to various stimuli, including elevated concentration of Aß, the peptide undergoes complex conformational rearrangements to form oligomer-competent or fibril-competent intermediates. Lipid rafts facilitate the production, aggregation, neuronal binding, and toxicity of Aß oligomers. High membrane cholesterol concentration promotes Aß incorporation into membranes and increases the cytosolic calcium concentration leading to cell death. Cyclodextrins (CDs) are well-known excipients used in the pharmaceutical field mainly for their inclusion properties. Several studies have demonstrated their potential use as neuroprotective agents due to their capability to extract and deplete cholesterol from cell membranes. It is known that the potential interactions between Aß and lipid rafts can change the activity of several signal transduction mechanisms such as cAMP response element binding (CREB) and CREB-related molecules such as mGluR5. Taking all these considerations into account, the aim of this work was to study the potential neuroprotective effects of HP-CD against Aß (1-42) induced AD against in vivo. To analyze the molecular effects of HP-CD on this model, we determined the levels of CREB and mGluR5 mRNA expression in rat hippocampus. According to our results Aß (1-42)-induced neurotoxicity changes the mRNA expression levels of genes of interest. HP-CD treatment against Aß (1-42) also regulates the expression levels of CREB and mGluR5 mRNA, and the regulated levels of CREB and mGluR5 may reflect potential neuroprotective effect of HP-CD.