NİTROSATİF STRES KÖKENLİ NÖRODEJENARATİF HASTALIKLARIN HÜCRESEL SİNYAL YOLAKLARININ ARABİDOPSİS THALİANA KULLANILARAK ARAŞTIRILMASI
Proje no. 495 · Durum: Kapanmış (Yayın bekleniyor) · 2018
Özet
<p>1.6 billion years ago, humans and Arabidopsis thaliana diverged evolutionarily. Despite this, there are conserved orthologs of human genes in Arabidopsis. For instance, the similarity rate between neurodegenerative disease genes in humans and their orthologs in Arabidopsis is known to be 71%, while the similarity rate with human cancer genes is 70%. Recent research aimed at better understanding neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD) has clearly demonstrated the importance of Arabidopsis in this field. In these studies, mutations in the PreP and DJ-1/PARK genes, which cause AD and PD diseases, have been shown to lead to similar formations in plants as in humans. However, these neurodegenerative diseases are not solely caused by mutations in the mentioned genes. Recent studies have found that an increase in the activation of the Glutamate Receptor (NMDAR) in the human brain cell membrane, triggering excessive accumulation of Ca2+ in the cytoplasm, leads to mitochondrial and endoplasmic reticulum (ER) stress caused by NO (nitric oxide) accumulation through S-nitrosylation of the protein disulfide isomerase (PDI) enzyme (binding of NO to cysteine thiol). This mitochondrial and ER stress has been found to be linked to neurodegenerative diseases like AD and PD. GLRs (Glutamate-like receptors) have been identified not only in mammals but also in all three domains of life. Studies on plants have shown that plant GLRs play roles in many pathways. However, there is no study on the GLR-mediated NO-related nitrosative stress and changes in organelles. In this study, we shed light on the roles and mechanisms of genes and proteins involved in a cellular pathway responsible for neurodegenerative diseases in humans, their orthologs in Arabidopsis, and the effects on the PDI enzyme caused by GLR-mediated NO accumulation. We also elucidate the mechanisms of organelle stress, as well as the relationship between Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and their effective antioxidant mechanisms in scavenging from cells, and the cell's redox balance. This study provides the first insights into these aspects.</p>