scholarly journals Neuroprotective effects of high affinity sigma 1 receptor selective compounds

2012 ◽  
Vol 1441 ◽  
pp. 17-26 ◽  
Author(s):  
Robert R. Luedtke ◽  
Evelyn Perez ◽  
Shao-Hua Yang ◽  
Ran Liu ◽  
Suwanna Vangveravong ◽  
...  
Keyword(s):  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
High Affinity ◽  
Sigma 1

Neuroprotective effects of sigma-1 receptor agonists against beta-amyloid-induced toxicity

Neuroreport ◽  
2005 ◽  
Vol 16 (11) ◽  
pp. 1223-1226 ◽  
Author(s):  
Agostino Marrazzo ◽  
Filippo Caraci ◽  
Elisa Trovato Salinaro ◽  
Tsung-Ping Su ◽  
Agata Copani ◽  
...  
Keyword(s):  
Beta Amyloid ◽  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
Receptor Agonists ◽  
Sigma 1

Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss

2015 ◽  
Vol 93 (5) ◽  
pp. 788-795 ◽  
Author(s):  
Daisuke Yamashita ◽  
Guang-wei Sun ◽  
Yong Cui ◽  
Shiro Mita ◽  
Naoki Otsuki ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Noise Induced Hearing Loss ◽  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
Sigma 1

Neuroprotective effects of the sigma-1 receptor ligand PRE-084 against excitotoxic perinatal brain injury in newborn mice

2012 ◽  
Vol 237 (2) ◽  
pp. 388-395 ◽  
Author(s):  
E. Griesmaier ◽  
A. Posod ◽  
M. Gross ◽  
V. Neubauer ◽  
K. Wegleiter ◽  
...  
Keyword(s):  
Brain Injury ◽  
Perinatal Brain Injury ◽  
Neuroprotective Effects ◽  
Receptor Ligand ◽  
Newborn Mice ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals Neuroprotective Effects of Sigma 1 Receptor Ligands on Motoneuron Death after Spinal Root Injury in Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6956
Author(s):  
Núria Gaja-Capdevila ◽  
Neus Hernández ◽  
Daniel Zamanillo ◽  
Jose Miguel Vela ◽  
Manuel Merlos ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Palliative Surgery ◽  
Lumbar Spinal Cord ◽  
Spinal Root ◽  
Post Injury ◽  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
Adult Mice ◽  
Root Injury ◽  
Sigma 1

Loss of motor neurons (MNs) after spinal root injury is a drawback limiting the recovery after palliative surgery by nerve or muscle transfers. Research based on preventing MN death is a hallmark to improve the perspectives of recovery following severe nerve injuries. Sigma-1 receptor (Sig-1R) is a protein highly expressed in MNs, proposed as neuroprotective target for ameliorating MN degenerative conditions. Here, we used a model of L4–L5 rhizotomy in adult mice to induce MN degeneration and to evaluate the neuroprotective role of Sig-1R ligands (PRE-084, SA4503 and BD1063). Lumbar spinal cord was collected at 7, 14, 28 and 42 days post-injury (dpi) for immunohistochemistry, immunofluorescence and Western blot analyses. This proximal axotomy at the immediate postganglionic level resulted in significant death, up to 40% of spinal MNs at 42 days after injury and showed markedly increased glial reactivity. Sig-1R ligands PRE-084, SA4503 and BD1063 reduced MN loss by about 20%, associated to modulation of endoplasmic reticulum stress markers IRE1α and XBP1. These pathways are Sig-1R specific since they were not produced in Sig-1R knockout mice. These findings suggest that Sig-1R is a promising target for the treatment of MN cell death after neural injuries.

scholarly journals Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 211 ◽  
Author(s):  
Maximilian Christ ◽  
Heike Huesmann ◽  
Heike Nagel ◽  
Andreas Kern ◽  
Christian Behl
Keyword(s):  
Clinical Investigation ◽  
Receptor Activation ◽  
Autophagic Flux ◽  
Neuroprotective Effects ◽  
Sigma 1 Receptor ◽  
C Elegans ◽  
Protein Clearance ◽  
Sigma 1

Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis of human neurodegenerative diseases and the modulation of autophagy as the protein clearance process has become one key pharmacological target. Due to the role of sigma-1 receptors (Sig-1R) in learning and memory, and the described pleiotropic neuroprotective effects in various experimental paradigms, Sig-1R activation is recognized as one potential approach for prevention and therapy of neurodegeneration and, interestingly, in amyotrophic lateral sclerosis associated with mutated Sig-1R, autophagy is disturbed. Here we analyzed the effects of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73), a muscarinic receptor ligand and Sig-1R agonist, on autophagy and proteostasis. We describe, at the molecular level, for the first time, that pharmacological Sig-1R activation a) enhances the autophagic flux in human cells and in Caenorhabditis elegans and b) increases proteostasis capacity, ultimately ameliorating paralysis caused by protein aggregation in C. elegans. ANAVEX2-73 is already in clinical investigation for the treatment of Alzheimer’s disease, and the novel activities of this compound on autophagy and proteostasis described here may have consequences for the use and further development of the Sig-1R as a drug target in the future. Moreover, our study defines the Sig-1R as an upstream modulator of canonical autophagy, which may have further implications for various conditions with dysfunctional autophagy, besides neurodegeneration.

scholarly journals Nitrile analogs of meperidine as high affinity and selective sigma-1 receptor ligands

2008 ◽  
Vol 43 (6) ◽  
pp. 1304-1308 ◽  
Author(s):  
Susan L. Mercer ◽  
Jamaluddin Shaikh ◽  
John R. Traynor ◽  
Rae R. Matsumoto ◽  
Andrew Coop
Keyword(s):  
Receptor Ligands ◽  
Sigma 1 Receptor ◽  
High Affinity ◽  
Sigma 1

scholarly journals Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening

2021 ◽  
Vol 22 (15) ◽  
pp. 8112
Author(s):  
Szabolcs Dvorácskó ◽  
László Lázár ◽  
Ferenc Fülöp ◽  
Márta Palkó ◽  
Zita Zalán ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Radioligand Binding ◽  
Binding Assays ◽  
Receptor Ligands ◽  
Sigma 1 Receptor ◽  
High Affinity ◽  
Ensemble Docking ◽  
Sigma 1 ◽  
Screening Protocol ◽  
Agonist And Antagonist

Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.

scholarly journals Cardioprotective Effect of Fluvoxamine, Sigma-1 Receptor High Affinity Agonist

2012 ◽  
Vol 132 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Hideaki Tagashira ◽  
Kohji Fukunaga
Keyword(s):  
Cardioprotective Effect ◽  
Sigma 1 Receptor ◽  
High Affinity ◽  
Sigma 1
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