فهرست مطالب naser sanchooli

This study aimed to investigate the association between Endoplasmic Reticulum autophagy (ER-phagy) and Alzheimer’s Disease (AD) by analyzing the expression patterns of related genes in animal models.

Microarray data of AD patients’ brain tissues were extracted from the Gene Expression Omnibus (GEO) database. These data were first analyzed in GEO2R online tool. Then, the expression of ER-phagy related genes were isolated and the protein interaction networks were plotted by STRING database for the genes with increased expression. Finally, the relationship between the genes that had significant increased expression were designed, and the expression of new identified genes in each study was examined. 

 All ethical principles were considered in this article. 

 Genes involved in ER-phagy showed a sporadic expression in different AD models. An increase in the expression of ER-phagy regulatory 1 (FAM134B) gene was observed in studies with the mutation in both Microtubule-associated Protein Tau (MAPT) and Amyloid Precursor Protein (APP) genes. Increase in the expression of NPC intracellular cholesterol transporter 1 (NPC1) gene was observed in two studies that had mutations in APP, Presenilin 1 (PSEN1) and MAPT genes. Moreover, SEC62 homolog and Cell Cycle Progression 1 (CCPG1) genes both showed decreased expression in one study. Finally, the expression of Reticulon 3 (RTN3) was not significant in any of the studies.

 The genes involved in ER-phagy have a sporadic expression in AD models, where only two genes FAM134B and NPC1 are involved in AD. The FAM134B gene seems to interact with the Wnk1 gene, which plays a role in cell survival and proliferation, in the hippocampus and forebrain. It also interacts with the Map1lc3b gene, which has a role in phagosome deletion and protein ubiquitination, in the forebrain. It also interacts with the Map1lc3b gene, which has a role in phagosome deletion and protein ubiquitination, in the forebrain. NPC1 had interaction with the Abcg1 gene, which activates lipid homeostasis, in the subventricular zone.

Quinazolinones are heterocyclic and water insoluble compounds with various pharmacological and biological characteristics (antibacterial, antiswelling, antifungal, parkinson and etc.). They are used for treatment HIV and cancer. This study investigated the effects of 4(3H) quinazlonones-2-ethyl-2-phenyl ethyl (QEPE) as a new quinazolinons compounds on the spleen and immunocompetent cells of newborn Balb/C mice. Pregnant mice were divided into 3 groups (n=10) of control, sham and experimental, received distilled water, methyl cellulose %0.05 (the solvent) and 100 mg/kg body weight (ip) of QEPE (most effective dose), respectively, on days 8 to 15 of gestation. Examinations indicated an increase in weight of spleen in experimental group. Pathological studies showed increase in capsule thickness and number of macrophage cells of experimental group. Statistical analysis showed significant differences in morphological studies between experimental, sham and control groups. The statistical data on capsule thickness and number of macrophage cells indicated significant differences between groups. Detailed observations showed an increase in the volume of monocyte, neutrophile and eosinophile, in response to QEPE, but the volume of lymphocyte and basophile were similar in experimental, control and sham groups. The damages caused by this dose of QEPE could have been the reason for the increase in the number of immonucompetent and macrophage cells. Some studies showed damages to the organs such as livers and hearts would lead to the increase in the thickness of spleen capsule, consequently, increase in its weight and leading to splenomegaly. So, QEPE can not be an appropriate candidate for drug development. QEPE in lower doses might be an appropriate candidate for increase of immune system resistance.