In vivo, Sig-1R ligand EST79232 had a more potent effect on preventing MN degeneration than EST79376. In contrast, the agonist EST79232 significantly increased MN survival in the three models of MN degeneration evaluated and had a mild beneficial effect on motor function in SOD1 G93A mice. The antagonist EST79376 preserved MNs in vitro and after spinal nerve injury but was not able to improve MN death in SOD1 G93A mice. We used an in vitro model of spinal cord organotypic cultures under chronic excitotoxicity and two in vivo models, the spinal nerve injury and the superoxide dismutase 1 (SOD1) G93A mice, to characterize the effects of these Sig-1R ligands on MN survival and modulation of glial reactivity. In this study, two novel synthesized Sig-1R ligands, coded EST79232 and EST79376, from the same chemical series, with the same scaffold and similar physicochemical properties but opposite functionality on Sig-1R, were evaluated as neuroprotective compounds to prevent MN degeneration. Previous studies have suggested that Sig-1R is a target to prevent MN degeneration. Sigma-1 receptor (Sig-1R) is a protein enriched in MNs, and mutations on its gene lead to various types of MND. Motor neuron diseases (MNDs) include sporadic and hereditary neurological disorders characterized by progressive degeneration of motor neurons (MNs). Authors may use MDPI'sĮnglish editing service prior to publication or during author revisions. Submitted papers should be well formatted and use good English. For details about the APC please see here. There is an Article Processing Charge (APC) for publication in this Please visit the Instructions for Authors page before submitting a manuscript. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. All manuscripts are thoroughly refereed through a single-blind peer-review process. Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. Research articles, review articles as well as short communications are invited. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. All submissions that pass pre-check are peer-reviewed. Manuscripts can be submitted until the deadline. Once you are registered, click here to go to the submission form. Manuscripts should be submitted online at by registering and logging in to this website. This Special Issue will collect data from the experts in the sigma receptor field with the aim of disseminating knowledge about these pluripotent proteins and advancing research toward their full understanding and possible therapeutic applications. Surprisingly, sigma receptors have been identified as host proteins for interaction with SARS-CoV-2 proteins, with one sigma ligand performing 20-fold better than hydroxychloroquine in the antiviral assays. The overexpression of this subtype in tumor tissues and its role in cell proliferation have mostly driven the research in the oncology field, but recent evidence has highlighted sigma-2 as the receptor responsible for the binding of Abeta oligomers to neurons one sigma-2 ligand is now in clinical trials for the treatment of Alzheimer’s disease. After diverse hypotheses, the sigma-2 subtype was recently identified as TMEM97, rejuvenating interest in sigma-2-related research. Drugs interacting with the sigma-1 subtype have potential for the treatment of CNS disfunctions, neurodegenerative diseases, pain, cocaine abuse, and tumors. Its recently obtained crystal structure, which shows a peculiar folding, will facilitate the understanding of the oligomerization/polymerization processes that address the sigma-1 receptor functions. The sigma-1 subtype has been defined as a pluripotent chaperone that interacts with several client proteins. Almost five decades after their discovery, the role of sigma receptors in health and disease is still an intriguing subject.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |