The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism
Abstract
The sigma-1 receptor, an endoplasmic reticulum-associated molecular chaperone, is attracting great interest as a potential target for neuroprotective treatments. We provide the first evidence that pharmacological modulation of this protein produces functional neurorestoration in experimental parkinsonism. Mice with intrastriatal 6-hydroxydopamine lesions were treated daily with the selective sigma-1 receptor agonist, PRE-084, for 5 weeks. At the dose of 0.3 mg/kg/day, PRE-084 produced a gradual and significant improvement of spontaneous forelimb use. The behavioural recovery was paralleled by an increased density of dopaminergic fibres in the most denervated striatal regions, by a modest recovery of dopamine levels, and by an upregulation of neurotrophic factors (BDNF and GDNF) and their downstream effector pathways (extracellular signal regulated kinases 1/2 and Akt). No treatment-induced behavioural-histological restoration occurred in sigma-1 receptor knockout mice subjected to 6-hydroxydopamine lesions and treated with PRE-084. Immunoreactivity for the sigma-1 receptor protein was evident in both astrocytes and neurons in the substantia nigra and the striatum, and its intracellular distribution was modulated by PRE-084 (the treatment resulted in a wider intracellular distribution of the protein). Our results suggest that sigma-1 receptor regulates endogenous defence and plasticity mechanisms in experimental parkinsonism. Boosting the activity of this protein may have disease-modifying effects in Parkinson's disease.
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Cites
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Neuroinflammation in Parkinson’s disease: A target for neuroprotection?
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Liberatore, G. T., Jackson-Lewis, V., Vukosavic, S., Mandir, A. S., Vila, M., McAuliffe, W. G., Dawson, V. L., Dawson, T. M., & Przedborski, S. (1999) · Nature Medicine · doi:10.1038/70978 · Cited by 1,046 · cited 2×
“mediators of nigrostriatal dopamine degeneration (Liberatore et al., 1999; Iravani et al., 2002; Cali et al., 2012), and neuroinflammation is widely recognized as an important contributor to”
BackgroundThe pharmacology of sigma-1 receptors.
Maurice, T., & Su, T.-P. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.07.001 · Cited by 654
Hayashi, T., & Su, T.-P. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.051284 · Cited by 262
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Low density of sigma1 receptors in early Alzheimer’s disease
Mishina, M., Ohyama, M., Ishii, K., Kitamura, S., Kimura, Y., Oda, K.-I., Kawamura, K., Sasaki, T., Kobayashi, S., Katayama, Y., et al. (2008) · Annals of Nuclear Medicine · doi:10.1007/s12149-007-0094-z · Cited by 172 · cited 1×
“…neuroprotective effects of sigma-1 receptor (Sig-1R) ligands in animal models of brain disorders, including Alzheimer’s disease (Jansen et al., 1993; Mishina et al., 2008), amyotrophic lateral sclerosis (Mancuso et al., 2012; Prause et al., 2013), and stroke (Harukuni et al., 2000; Ajmo et al.,…”
BackgroundVillard, V., Espallergues, J., Keller, E., Vamvakides, A., & Maurice, T. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881110379286 · Cited by 139
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Self-citation
Cited by
The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems
Su, T.-P., Su, T.-C., Nakamura, Y., & Tsai, S.-Y. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.01.003 · Cited by 320
Fieblinger, T., Graves, S. M., Sebel, L. E., Alcacer, C., Plotkin, J. L., Gertler, T. S., Chan, C. S., Heiman, M., Greengard, P., Cenci, M. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6316 · Cited by 295
Self-citationVelazquez, R., Ferreira, E., Knowles, S., Fux, C., Rodin, A., Winslow, W., & Oddo, S. (2019) · Aging Cell · doi:10.1111/acel.13037 · Cited by 156
Current disease modifying approaches to treat Parkinson’s disease
Lindholm, D., Mäkelä, J., Di Liberto, V., Mudò, G., Belluardo, N., Eriksson, O., & Saarma, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2101-1 · Cited by 99
Sigma-1 receptor: a potential therapeutic target for traumatic brain injury
Shi, M., Chen, F., Chen, Z., Yang, W., Yue, S., Zhang, J., & Chen, X. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.685201 · Cited by 58
Metadata
- Authors
- Francardo, V., Bez, F., Wieloch, T., Nissbrandt, H., Ruscher, K., & Cenci, M. A.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-04-22
- Volume
- 137
- Issue
- 7
- Pages
- 1998-2014
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2060650451
- Cited by
- 206
- References
- 9
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- closed
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