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Cited by 32Amyotrophic Lateral Sclerosis ResearchPharmacological Receptor Mechanisms and EffectsAlzheimer's disease research and treatments

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Sigma-1 Receptor is a Pharmacological Target to Promote Neuroprotection in the SOD1G93A ALS Mice

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Gaja-Capdevila, Núria, Hernández, Neus, Navarro, Xavier, Herrando-Grabulosa, Mireia·2021·Frontiers in Pharmacology
DOI 10.3389/fphar.2021.780588PMC PMC8702863
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Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the death of motoneurons (MNs) with a poor prognosis. There is no available cure, thus, novel therapeutic targets are urgently needed. Sigma-1 receptor (Sig-1R) has been reported as a target to treat experimental models of degenerative diseases and, importantly, mutations in the Sig-1R gene cause several types of motoneuron disease (MND). In this study we compared the potential therapeutic effect of three Sig-1R ligands, the agonists PRE-084 and SA4503 and the antagonist BD1063, in the SOD1 G93A mouse model of ALS. Pharmacological administration was from 8 to 16 weeks of age, and the neuromuscular function and disease progression were evaluated using nerve conduction and rotarod tests. At the end of follow up (16 weeks), samples were harvested for histological and molecular analyses. The results showed that PRE-084, as well as BD1063 treatment was able to preserve neuromuscular function of the hindlimbs and increased the number of surviving MNs in the treated female SOD1 G93A mice. SA4503 tended to improve motor function and preserved neuromuscular junctions (NMJ), but did not improve MN survival. Western blot analyses revealed that the autophagic flux and the endoplasmic reticulum stress, two pathways implicated in the physiopathology of ALS, were not modified with Sig-1R treatments in SOD1 G93A mice. In conclusion, Sig-1R ligands are promising tools for ALS treatment, although more research is needed to ascertain their mechanisms of action.

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  • Pridopidine, a Sigma-1R agonist, has been enrolled in a Phase III clinical trial for treatment of ALS.

    “Pridopidine, a Sigma-1R agonist, has been enrolled in a Phase III clinical trial for treatment of ALS.579”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [579]

    The Introduction (page not provided) calls pridopidine a Sig-1R agonist and says it is being tested in a clinical trial for ALS (NCT04615923). It does not identify that trial as Phase III, so the claimed trial phase is unsupported by our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Metadata

Authors
Gaja-Capdevila, N., Hernández, N., Navarro, X., & Herrando-Grabulosa, M.
Affiliations
Universitat Autònoma de Barcelona (ES)
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2021-12-10
Volume
12
Pages
780588-780588
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2021.780588
PMC
PMC8702863
OpenAlex
W4200441325
Cited by
32
References
2
Citations by year
2026: 5 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 4
FWCI
2.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministerio de Ciencia, Innovación y Universidades
  • Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
  • Instituto de Salud Carlos III
Topics
  • Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords
sigma-1 receptor, amyotrophic lateral sclerosis, SOD1 G93A mice, motoneuron survival, PRE-084, SA4503, neuromuscular junction, autophagy, endoplasmic reticulum stress, neuroprotection, motor function

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