Caffeine for Prevention of Alzheimer’s Disease: Is the A2A Adenosine Receptor Its Target?
Abstract
:1. Introduction
2. Caffeine Metabolism
3. Alzheimer’s Disease (AD)
4. A2A Adenosine Receptors in AD
5. Caffeine and A2AR: In Vitro and In Vivo Models of AD
6. Caffeine and AD: Clinical Studies
7. AD, Caffeine, and Gender Differences
8. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Experimental Model of AD | Main Results | Mechanisms of Neuroprotection | References |
---|---|---|---|
APPsw transgenic (Tg) mice SweAPP N2a neuronal cultures | Caffeine induces cognitive protection in spatial learning/reference memory, working memory, and recognition/identification tests | ↓PS1 ↓BACE ↓Aβ ↓Aβ | [79] |
Adult male Wistar rats with sporadic AD | Caffeine prevents Streptozotocin-induced memory decline, neuronal damage, and A2AR upregulation | ND | [82] |
18–19 month-old APPsw mice | Caffeine improves working memory | ↓PS1 ↓BACE1 ↓Aβ | [91] |
AD Tg mice | Therapeutic value of caffeine against AD | ↓Aβ | [92] |
THY-Tau22 Tg mouse | Caffeine improves spatial memory | ↓ Tau phosphorylation ↓ Proinflammatory and oxidative stress markers | [93] |
CF1 adult mice injected with Aβ | Caffeine or selective A2AR treatment showed a protective effect against cognitive decline | ND | [94] |
Primary rat cerebellar neurons | Caffeine shows neuroprotective effects through A2AR antagonism | ↓Aβ-induced neuronal cell death | [96] |
WT Zebrafish | Caffeine pre-treatment prevented scopolamine-induced amnesia | A2AR antagonism | [97] |
Male CF1 mice | Caffeine increases memory and cognitive functions scopolamine-decreased | ND | [98] |
A2AR KO mice | Caffeine normalizes memory impairment induced by TBI-mediated A2AR activation | ↓Tau phosphorylation | [100] |
Young and aged male Swiss mice | Caffeine decreases A2AR and the number of pyknotic aged neurons | ND | [101] |
Adult male C57bl\6j mice | Caffeine increases the metabolic competence of synapses | ND | [102] |
PS1/APP double Tg mice | Caffeine increases memory capability | ↑BDNF ↑TrkB | [104] |
Adult male albino Sprague-Dawley rats | Caffeine has a potentially good protective effect against AD induced by AlCl3 | ↑BDNF ↑TrkB | [105] |
C57BL/6N male mice | Caffeine may regulate oxidative stress, neuroinflammation, and synaptic dysfunctions in LPS-injected mouse brains | ↑Nrf2/TLR4 | [106] |
Adult male Sprague-Dawley rats | Caffeine has a beneficial effect against artificial senescence in mice induced by D-galactose | ↓p-JNK, COX-2, NOS-2, TNFα and IL-1β | [108] |
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Merighi, S.; Travagli, A.; Nigro, M.; Pasquini, S.; Cappello, M.; Contri, C.; Varani, K.; Vincenzi, F.; Borea, P.A.; Gessi, S. Caffeine for Prevention of Alzheimer’s Disease: Is the A2A Adenosine Receptor Its Target? Biomolecules 2023, 13, 967. https://doi.org/10.3390/biom13060967
Merighi S, Travagli A, Nigro M, Pasquini S, Cappello M, Contri C, Varani K, Vincenzi F, Borea PA, Gessi S. Caffeine for Prevention of Alzheimer’s Disease: Is the A2A Adenosine Receptor Its Target? Biomolecules. 2023; 13(6):967. https://doi.org/10.3390/biom13060967
Chicago/Turabian StyleMerighi, Stefania, Alessia Travagli, Manuela Nigro, Silvia Pasquini, Martina Cappello, Chiara Contri, Katia Varani, Fabrizio Vincenzi, Pier Andrea Borea, and Stefania Gessi. 2023. "Caffeine for Prevention of Alzheimer’s Disease: Is the A2A Adenosine Receptor Its Target?" Biomolecules 13, no. 6: 967. https://doi.org/10.3390/biom13060967
APA StyleMerighi, S., Travagli, A., Nigro, M., Pasquini, S., Cappello, M., Contri, C., Varani, K., Vincenzi, F., Borea, P. A., & Gessi, S. (2023). Caffeine for Prevention of Alzheimer’s Disease: Is the A2A Adenosine Receptor Its Target? Biomolecules, 13(6), 967. https://doi.org/10.3390/biom13060967