Table 2.
Summary of recent animal and cell culture studies investigating the relationship between methylxanthines and Alzheimer´s disease (AD). FAD: familial Alzheimer´s disease. A1AR: adenosine A1 receptor. A2AR: adenosine A2 receptor. LPS: lipopolysaccharide.
| Author | Year | Used Model | Substance | Outcome |
|---|---|---|---|---|
| Liang Jin et al. [27] | 2020 | APP/PS1 mice | caffeine | intestinal permeability and oral absorption were not affected in the FAD mouse model |
| Zappettini et al. [28] | 2019 | THY-Tau22 mice | caffeine | consumption during pregnancy accelerates the development of cognitive deficits in offspring in a model of tauopathy |
| Yoneda et al. [30] | 2017 | C57BL/6NCr mice | theobromine | up-regulated cerebral brain-derived neurotrophic factor and facilitated motor learning |
| Orr et al. [31] |
2018 | mice with AD-like amyloid plaque pathology | istradefylline | reduced memory deficits |
| Franco et al. [32] |
2020 | primary cultures of neurons and microglia from control and APPSw,Ind mice | antagonists of A2AR | high levels of theobromine detected in CSF are associated with clinical progression to dementia |
| Gastaldo et al. [33] | 2020 | synthetic brain membranes | caffeine | caffeine is able to affect Aβ peptide aggregation in AD through a membrane-mediated pathway |
| Gupta et al. [35] | 2019 | in silico study | caffeine | disorganization of cross-β structures of Aβ17-42 fibrils in the presence of caffeine |
| Janitschke et al. [21] | 2019 | SH-SY5Y cells | caffeine, theobromine, theophylline, pentoxifylline, propentofylline | MTX reduce Aβ levels via pleiotropic molecular mechanisms and decrease oxidative stress, cholesterol levels and Aβ aggregation |
| Fabiani et al. [36] | 2018 | AchR-rich membrane fragments from T. californica and HEK293 cells | caffeine | pharmacological activity of caffeine in the cholinergic system |
| Kumar et al. [37] | 2019 | primary hippocampal neurons | caffeine | AchE inhibitory potential, improved neuronal survival and protection from neurodegeneration |
| Badshah et al. [41] | 2019 | LPS-injected mouse model | caffeine | prevention of LPS-induced oxidative stress and suppression of inflammatory mediators |
| Khan et al. [42] | 2019 | HT-22 and BV-2 cells, B57BL/6N mice |
caffeine | modulation of cadmium-induced oxidative stress, neuroinflammation, and cognitive impairments by regulating nrf-2/ho-1 in vivo and in vitro |
| Zhao et al. [45] | 2020 | HEK293 cells | caffeine | inhibition of notum activity by binding at the catalytic pocket |
| Nabbi-Schroeter et al. [48] | 2018 | Sprague-Dawley rats | caffeine | no long-persistent upregulation of functionally available A1Ars under their conditions |
| Mendiola-Precoma et al. [49] | 2017 | rat brain AD model | theobromine | theobromine-induced changes in A1AR expression and distribution |
| Ciaramelli et al. [51] | 2021 | SH-SY5Y cells | theobromine | theobromine hinders Aβ peptide aggregation and toxicity |
| Janitschke et al. [52] | 2020 | SH-SY5Y cells | caffeine, theobromine, theophylline, pentoxifylline, propentofylline | different or inverse transcriptional regulatory effects of caffeine compared to the other tested MTX on AD-related genes |