Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy
Open accessAbstract
Since proving adenosine triphosphate (ATP) functions as a neurotransmitter in neuron/glia interactions, the purinergic system has been more intensely studied within the scope of the central nervous system. In neurological disorders with associated motor symptoms, including Parkinson's disease (PD), motor neuron diseases (MND), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's Disease (HD), restless leg syndrome (RLS), and ataxias, alterations in purinergic receptor expression and activity have been noted, indicating a potential role for this system in disease etiology and progression. In neurodegenerative conditions, neural cell death provokes extensive ATP release and alters calcium signaling through purinergic receptor modulation. Consequently, neuroinflammatory responses, excitotoxicity and apoptosis are directly or indirectly induced. This review analyzes currently available data, which suggests involvement of the purinergic system in neuro-associated motor dysfunctions and underlying mechanisms. Possible targets for pharmacological interventions are also discussed.
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In animal models for neurodegeneration, P2X7 receptor antagonism exerted beneficial anti-inflammatory effects, indicating that P2X7 receptor activation and subsequent neuroinflammation is tightly related to neurodegeneration worsening.
“In animal models for neurodegeneration P2X7 receptor antagonism exerted beneficial anti-inflammatory effects [138, 139], indicating that P2X7 receptor activation and subsequent neuroinflammation is tightly related to neurodegeneration worsening.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [138]
In neurodegenerative diseases, cell death is accompanied by neuroinflammatory processes and massive ATP release.
“In neurodegenerative diseases, cell death is accompanied by neuroinflammatory processes and massive ATP release [138].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [138]
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Purine nucleosides in neuroregeneration and neuroprotection
Ribeiro, F. F., Xapelli, S., Miranda‐Lourenço, C., Tanqueiro, S. R., Fonseca‐Gomes, J., Diógenes, M. J., Ribeiro, J. A., & Sebastião, A. M. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.11.006 · Cited by 74 · see citing works
Blum, D. L., Gall, D., Galas, M., d’Alcantara, P., Bantubungi, K., & Schiffmann, S. N. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-09122.2002 · Cited by 73 · see citing works
Xu, P., Rosen, K. M., Hedstrom, K. L., Rey, O., Guha, S., Hart, C., & Corfas, G. (2013) · Glia · doi:10.1002/glia.22491 · Cited by 73 · see citing works
Zhu, Y., & Kimelberg, H. K. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00241.x · Cited by 73 · see citing works
Association between caffeine intake and age at onset in Huntington's disease
Simonin, C., Duru, C., Salleron, J., Hincker, P., Charles, P., Delval, A., Youssov, K., Burnouf, S., Azulay, J., Verny, C., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.05.013 · Cited by 73 · see citing works
Gu, B. J., Field, J., Dutertre, S., Ou, A., Kilpatrick, T. J., Lechner‐Scott, J., Scott, R. J., Lea, R. A., Taylor, B. V., Stankovich, J. M., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv278 · Cited by 73 · see citing works
P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis.
Amadio, S., Montilli, C., Magliozzi, R., Bernardi, G., Reynolds, R., & Volonte, C. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhp193 · Cited by 73 · see citing works
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The P2X7 Receptor: Central Hub of Brain Diseases
Andrejew, R., Oliveira-Giacomelli, Á., Ribeiro, D. E., Glaser, T., Arnaud-Sampaio, V. F., Lameu, C., & Ulrich, H. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00124 · Cited by 162 · see citing works
Self-citationHyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology
Ribeiro, D. E., Oliveira-Giacomelli, Á., Glaser, T., Arnaud-Sampaio, V. F., Andrejew, R., Dieckmann, L., Baranova, J., Lameu, C., Ratajczak, M. Z., & Ulrich, H. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00965-3 · Cited by 145 · see citing works
Self-citationOliveira-Giacomelli, Á., M. Albino, C., de Souza, H. D. N., Corrêa-Velloso, J., de Jesus Santos, A. P., Baranova, J., & Ulrich, H. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00476 · Cited by 60 · see citing works
Self-citationErnest James Phillips, T., & Maguire, E. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.652593 · Cited by 33 · see citing works
- Authors
- Oliveira-Giacomelli, Á., Naaldijk, Y., Sardá-Arroyo, L., Gonçalves, M. C. B., Corrêa-Velloso, J., Pillat, M. M., de Souza, H. D. N., & Ulrich, H.
- Affiliations
- Universidade de São Paulo (BR)
- Universidade Federal de São Paulo (BR)
- Corresponding author
- Ulrich, Henning
- ORCID
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2018-04-10
- Volume
- 9
- Pages
- 325-325
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC5902708
- OpenAlex
- W2796748561
- Cited by
- 50
- References
- 317
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 8 · 2018: 3
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/50880-4, 2012/20685-5, 2013/25338-4, 2015/19478-3, 2015/14343-2)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (306429/2013-6, 141979/2014-3, 870458/1997-3)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- purinergic receptors, ATP as neurotransmitter, Parkinson's disease, motor neuron disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, restless legs syndrome, ataxia, neuroinflammation, excitotoxicity, apoptosis, calcium signaling, neurodegeneration, therapeutic target
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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