Journal ArticleDOI
Theobromine-Induced Changes in A1 Purinergic Receptor Gene Expression and Distribution in a Rat Brain Alzheimer's Disease Model.
Jesus Mendiola-Precoma,Karla Padilla,Alfredo Rodríguez-Cruz,Laura C. Berumen,Ricardo Miledi,Guadalupe García-Alcocer +5 more
TLDR
The results indicated that the fat-enriched diet resulted in a long-term deterioration in cognitive and memory functions, and Interestingly, theobromine, at both concentrations tested, restored A1 receptor levels and improved cognitive functions and Aβ levels for a dose of 30 mg/L drinking water.Abstract:
Dementia caused by Alzheimer's disease (AD) is mainly characterized by accumulation in the brain of extra- and intraneuronal amyloid-β (Aβ) and tau proteins, respectively, which selectively affect specific regions, particularly the neocortex and the hippocampus. Sporadic AD is mainly caused by an increase in apolipoprotein E, a component of chylomicrons, which are cholesterol transporters in the brain. Recent studies have shown that high lipid levels, especially cholesterol, are linked to AD. Adenosine is an atypical neurotransmitter that regulates a wide range of physiological functions by activating four P1 receptors (A1, A2A, A2B, and A3) and P2 purinergic receptors that are G protein-coupled. A1 receptors are involved in the inhibition of neurotransmitter release, which could be related to AD. The aim of the present work was to study the effects of a lard-enriched diet (LED) on cognitive and memory processes in adult rats (6 months of age) as well as the effect of theobromine on these processes. The results indicated that the fat-enriched diet resulted in a long-term deterioration in cognitive and memory functions. Increased levels of Aβ protein and IL-1β were also observed in the rats fed with a high-cholesterol diet, which were used to validate the AD animal model. In addition, the results of qPCR and immunohistochemistry indicated a decrease in gene expression and distribution of A1 purinegic receptor, respectively, in the hippocampus of LED-fed rats. Interestingly, theobromine, at both concentrations tested, restored A1 receptor levels and improved cognitive functions and Aβ levels for a dose of 30 mg/L drinking water.read more
Citations
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Journal ArticleDOI
Medicinal Chemistry and Therapeutic Potential of Agonists, Antagonists and Allosteric Modulators of A1 Adenosine Receptor: Current Status and Perspectives.
TL;DR: Partial agonists of A1 AR have been found to be beneficial in enhancing insulin sensitivity and subsequently reducing blood glucose level, while avoiding severe CVS side effects and tachyphylaxis, and allosteric enhancer of A 1 AR is found to have potential for the treatment of neuropathic pain.
Journal ArticleDOI
Adenosine Augmentation Evoked by an ENT1 Inhibitor Improves Memory Impairment and Neuronal Plasticity in the APP/PS1 Mouse Model of Alzheimer’s Disease
Chia-Chia Lee,Ching-Pang Chang,Chun-Jung Lin,Hsing-Lin Lai,Yu-Han Kao,Sin-Jhong Cheng,Hui-Mei Chen,Yu-Ping Liao,Emilie Faivre,Luc Buée,David Blum,Jim-Min Fang,Yijuang Chern +12 more
TL;DR: It is suggested that modulation of adenosine homeostasis by J4 is beneficial in a mouse model of AD, which provides a potential therapeutic strategy to delay the progression of AD.
Journal ArticleDOI
Exploring cocoa properties: is theobromine a cognitive modulator?
TL;DR: The conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.
Journal ArticleDOI
Purinergic signaling in Alzheimer's disease.
TL;DR: This review focuses on neuroinflammatory signaling mediated by purinergic receptors (P1 adenosine receptors, P2X ATP-gated ion channels and G protein-coupled P2Y nucleotide receptors) and how therapeutic modulation of purinerential signaling influences disease progression in AD patients and animal models of AD.
Journal ArticleDOI
Methylxanthines and Neurodegenerative Diseases: An Update.
Daniel Janitschke,Anna A. Lauer,Cornel M Bachmann,Heike S. Grimm,Tobias Hartmann,Marcus O. W. Grimm +5 more
TL;DR: In this paper, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated, such as adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation.
References
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Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
TL;DR: The A β-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk are discussed, and how to design effective strategies for AD therapy by targeting ApO-E is considered.
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Epidemiology of Alzheimer Disease
Richard Mayeux,Yaakov Stern +1 more
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Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images.
Rachael Brown,Rachael Brown,Cheree James,Luke A. Henderson,Vaughan G. Macefield,Vaughan G. Macefield +5 more
TL;DR: It is concluded that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images.
Journal ArticleDOI
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
TL;DR: There is substantial evidence that differential effects of apoE isoform on AD risk are influenced by the ability of apOE to affect Aβ aggregation and clearance in the brain.