The DOI matches its Crossref record; 343 of the 343 references it cites were found in a registry or an index.
Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade
Open accessAbstract
Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A(1) receptors (A(1)Rs) and the less abundant, but widespread, facilitatory A(2A)Rs. It is commonly assumed that A(1)Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A(1)R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A(1)Rs in chronic noxious situations. In contrast, A(2A)Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A(2A)R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A(2A)R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A(2A)R blockade compared to A(1)R activation does not mean that A(1)R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A(2A)R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A(1)Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.
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Cited by
How does adenosine control neuronal dysfunction and neurodegeneration?
Cunha, R. A. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13724 · Cited by 441
Self-citationAdenosine receptors and brain diseases: neuroprotection and neurodegeneration
Gomes, C. V., Kaster, M. P., Tomé, A. R., Agostinho, P. M., & Cunha, R. A. (2011) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.12.001 · Cited by 419
Self-citationCanas, P. M., Porciúncula, L. O., Cunha, G. M. A., Silva, C. G., Machado, N. J., Oliveira, J. M. A., Oliveira, C. R., & Cunha, R. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3728-09.2009 · Cited by 357
Self-citationAdenosine, energy metabolism and sleep homeostasis
Porkka-Heiskanen, T., & Kalinchuk, A. V. (2011) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2010.06.005 · Cited by 328
Kaster, M. P., Machado, N. J., Silva, H. B., Nunes, A., Ardais, A. P., Santana, M., Baqi, Y., Müller, C. E., Rodrigues, A. L. S., Porciúncula, L. O., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423088112 · Cited by 312
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Metadata
- Authors
- Cunha, R. A.
- Venue
- Purinergic Signalling
- Published
- 2005-03-17
- Volume
- 1
- Issue
- 2
- Pages
- 111-134
- ISSN
- 1573-9538 (ISSN-L)
- 1573-9546
- OpenAlex
- W2016036161
- Cited by
- 537
- References
- 343
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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