Role of σ1 Receptors in Learning and Memory and Alzheimer’s Disease-Type Dementia

Maurice, Tangui; Goguadze, Nino

doi:10.1007/978-3-319-50174-1_15

Cited by 30 publications

(15 citation statements)

References 143 publications

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“…The Sigma-1 receptor is considered a unique ligand-operated chaperone protein which regulates protein folding/degradation, ER/oxidative stress, and cell survival (Hayashi, 2015). Sigma-1 receptor ligands have long been expected to serve as drugs for the treatment of human diseases such as neurodegenerative disorders, depression, chronic pain, drug abuse, retinal disease, and cancer (Cobos et al, 2008; Katz et al, 2017; Kim and Maher, 2017; Maurice and Goguadze, 2017a,b; Merlos et al, 2017a,b; Sabino et al, 2017; Sanchez-Fernandez et al, 2017; Smith et al, 2018). Two subtypes of Sigma receptors have been identified, Sigma-1 and Sigma-2 (Hellewell et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Trends in Sigma-1 Receptor Research: A 25-Year Bibliometric Analysis

Romero

Portillo‐Salido

2019

Front. Pharmacol.

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Purpose: There are previous reviews focused on Sigma-1 receptor but no bibliometric studies examining this field as a whole. This article aims to present a global view of Sigma-1 receptor research and its intellectual structure. Methods: We used bibliometric indicators of a basic nature as well as techniques for the visualization and analysis of networks of scientific information extracted from Scopus database. Results: In total, 1,102 articles from 1992 to 2017 were identified. The growth in the production of articles is not constant over time, with periods of stagnation of approximately 5 years. Only 247 authors have five or more publications. The authors appear grouped in relatively independent clusters, thus suggesting a low level of collaborations between those dedicated to the Sigma-1 receptor. The United States was the country with the highest production followed by Japan and Germany. Spain, Japan, and Italy showed the highest per million inhabitants ratio. The highest citation/article ratio was reached in France, United States, and Canada. The leading institutions were the University of Münster, the National Institutes of Health, ESTEVE, and INSERM. The top authors in number of publications were Wünsch-B, Schepmann-D, and Maurice-T. Hayashi-T, Su-TP and Bowen-WD showed the highest citations per article. The article by Hayashi-T and Su-TP in Cell (2007) describing the Sigma-1 receptor as a chaperone protein is the top cited reference. Cluster labeling from author co-citation analysis shows that research has been focused on specific diseases such as addiction, neuroprotection and neurodegenerative diseases, psychiatric disorders, and pain. High-frequency terms in author keywords suggest that the research efforts in some areas such as neuroimaging, cocaine addiction or psychiatric disorders have declined over time, while others such as neurodegenerative diseases or pain are currently most popular. Perspective: A greater involvement of the scientific community, with an increase in the scientific production related to Sigma-1, is desirable. Additional boost needed to improve research performance is likely to come from combining data from different laboratories to overcome the limitations of individual approaches. The resulting maps are a useful and attractive tool for the Sigma-1 receptor research community, as they reveal the main lines of exploration at a glance.

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Section: Introductionmentioning

confidence: 99%

Trends in Sigma-1 Receptor Research: A 25-Year Bibliometric Analysis

Romero

Portillo‐Salido

2019

Front. Pharmacol.

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“…In general, deficits in Sig-1R expression or activity are linked to neurodegeneration and the activation of Sig-1R is associated with neuroprotection in different in vitro and in vivo models, employing different types of pharmacological Sig-1R activators with different pharmacological profiles [15,23]. The pharmacological activation of Sig-1R leads to pluripotent modulatory downstream effects, and incorrect function of Sig-1R is strongly suggested to be also involved in the pathogenesis of neurodegeneration [24].…”

Section: Introductionmentioning

confidence: 99%

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

Christ

Huesmann

Nagel

et al. 2019

Cells

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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.

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“…Detailed coverage of these other targets is outside the scope of this review, but their importance is evident. With the aim of helping to expand their corresponding investigation, we point out a few interesting findings and reviews for more information: allosteric modulators of β‐secretase (BACE), allosteric modulators of acetylcholinesterase (AChE), and allosteric modulators of σ1 receptors …”

Section: Discussionmentioning

confidence: 99%

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

et al. 2019

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Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β‐amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.

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Role of σ1 Receptors in Learning and Memory and Alzheimer’s Disease-Type Dementia

Cited by 30 publications

References 143 publications

Trends in Sigma-1 Receptor Research: A 25-Year Bibliometric Analysis

Trends in Sigma-1 Receptor Research: A 25-Year Bibliometric Analysis

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

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

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