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Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection.
Adv Exp Med Biol. 2017; 964:133-152.AE

Abstract

Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity. Here, we summarize their neuroprotective and neurorestorative effects in different animal models of acute brain injury and chronic neurodegenerative diseases, and highlight their potential role in mitigating disease. Notably, current data suggest that sigma-1 receptor dysfunction worsens disease progression, whereas enhancement amplifies pre-existing functional mechanisms of neuroprotection and/or restoration to slow disease progression. Collectively, the data support a model of the sigma-1 receptor as an amplifier of intracellular signaling, and suggest future clinical applications of sigma-1 ligands as part of multi-therapy approaches to treat neurodegenerative diseases.

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Authors+Show Affiliations

Nguyen L
Department of Behavioral Medicine and Psychiatry, School of Medicine, West Virginia University, 930 Chestnut Ridge Road, Morgantown, WV, 26506, USA. Department of Pharmaceutical Sciences, School of Pharmacy, One Medical Center, West Virginia University, Morgantown, WV, 26506, USA.
Lucke-Wold BP
Graduate Program in Neuroscience, School of Medicine, West Virginia University, One Medical Center Drive, Morgantown, WV, 26506, USA.
Mookerjee S
College of Pharmacy, Touro University California, 1310 Club Drive, Vallejo, CA, 94592, USA.
Kaushal N
Takeda California, Inc., San Diego, CA, 92121, USA.
Matsumoto RR
Department of Behavioral Medicine and Psychiatry, School of Medicine, West Virginia University, 930 Chestnut Ridge Road, Morgantown, WV, 26506, USA. rae.matsumoto@tu.edu. College of Pharmacy, Touro University California, 1310 Club Drive, Vallejo, CA, 94592, USA. rae.matsumoto@tu.edu.

MeSH

AnimalsBrainHumansLigandsMolecular ChaperonesNeurodegenerative DiseasesNeuroprotectionNeuroprotective AgentsReceptors, sigma

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28315269

Citation

Nguyen, Linda, et al. "Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection." Advances in Experimental Medicine and Biology, vol. 964, 2017, pp. 133-152.
Nguyen L, Lucke-Wold BP, Mookerjee S, et al. Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection. Adv Exp Med Biol. 2017;964:133-152.
Nguyen, L., Lucke-Wold, B. P., Mookerjee, S., Kaushal, N., & Matsumoto, R. R. (2017). Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection. Advances in Experimental Medicine and Biology, 964, 133-152. https://doi.org/10.1007/978-3-319-50174-1_10
Nguyen L, et al. Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection. Adv Exp Med Biol. 2017;964:133-152. PubMed PMID: 28315269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sigma-1 Receptors and Neurodegenerative Diseases: Towards a Hypothesis of Sigma-1 Receptors as Amplifiers of Neurodegeneration and Neuroprotection. AU - Nguyen,Linda, AU - Lucke-Wold,Brandon P, AU - Mookerjee,Shona, AU - Kaushal,Nidhi, AU - Matsumoto,Rae R, PY - 2017/3/19/entrez PY - 2017/3/21/pubmed PY - 2017/9/28/medline KW - Alzheimer’s disease KW - Amyotrophic lateral sclerosis KW - Neurorestoration KW - Parkinson’s disease KW - Stroke SP - 133 EP - 152 JF - Advances in experimental medicine and biology JO - Adv Exp Med Biol VL - 964 N2 - Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity. Here, we summarize their neuroprotective and neurorestorative effects in different animal models of acute brain injury and chronic neurodegenerative diseases, and highlight their potential role in mitigating disease. Notably, current data suggest that sigma-1 receptor dysfunction worsens disease progression, whereas enhancement amplifies pre-existing functional mechanisms of neuroprotection and/or restoration to slow disease progression. Collectively, the data support a model of the sigma-1 receptor as an amplifier of intracellular signaling, and suggest future clinical applications of sigma-1 ligands as part of multi-therapy approaches to treat neurodegenerative diseases. SN - 0065-2598 UR - https://www.unboundmedicine.com/medline/citation/28315269/Sigma_1_Receptors_and_Neurodegenerative_Diseases:_Towards_a_Hypothesis_of_Sigma_1_Receptors_as_Amplifiers_of_Neurodegeneration_and_Neuroprotection_ L2 - https://dx.doi.org/10.1007/978-3-319-50174-1_10 DB - PRIME DP - Unbound Medicine ER -