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Adenosine and Adenosine A2AReceptors as Targets for the Treatment of Niemann Pick Type C Disease 腺苷和腺苷a2a受体作为治疗C型尼曼匹克病的靶点
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-09-17 DOI: 10.1089/caff.2019.0014
FerranteAntonella, VisentinSergio, De NuccioChiara, MartireAlberto, PopoliPatrizia
Niemann Pick type C (NPC) is a rare neurovisceral disorder characterized by progressive hepatosplenomegaly, neurodegeneration, and premature death; it is caused by mutations in genes coding for two...
Niemann Pick C型(NPC)是一种罕见的神经内脏疾病,以进行性肝脾肿大、神经变性和过早死亡为特征;它是由编码两个基因的基因突变引起的。
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引用次数: 0
Adenosine: A Complex Role in Neurodegeneration 腺苷:在神经变性中的复杂作用
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-09-17 DOI: 10.1089/caff.2019.29015.dbl
D. Blum
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引用次数: 0
Novel Players in the Aging Synapse: Impact on Cognition. 衰老突触中的小说玩家:对认知的影响。
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-09-01 Epub Date: 2019-09-17 DOI: 10.1089/caff.2019.0013
Mariana Temido-Ferreira, Joana E Coelho, Paula A Pousinha, Luísa V Lopes

While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho- and electrophysiological alterations that occur in the major synapse of this network-the glutamatergic-deserve special attention. We guide you through the hippocampal anatomy, circuitry, and function in physiological context and focus on alterations in neuronal morphology, calcium dynamics, and plasticity induced by aging and Alzheimer's disease (AD). We provide state-of-the art knowledge on glutamatergic transmission and discuss implications of these novel players for intervention. A link between regular consumption of caffeine-an adenosine receptor blocker-to decreased risk of AD in humans is well established, while the mechanisms responsible have only now been uncovered. We review compelling evidence from humans and animal models that implicate adenosine A2A receptors (A2AR) upsurge as a crucial mediator of age-related synaptic dysfunction. The relevance of this mechanism in patients was very recently demonstrated in the form of a significant association of the A2AR-encoding gene with hippocampal volume (synaptic loss) in mild cognitive impairment and AD. Novel pathways implicate A2AR in the control of mGluR5-dependent NMDAR activation and subsequent Ca2+ dysfunction upon aging. The nature of this receptor makes it particularly suited for long-term therapies, as an alternative for regulating aberrant mGluR5/NMDAR signaling in aging and disease, without disrupting their crucial constitutive activity.

虽然神经元损失长期以来一直被认为是年龄相关认知能力下降的主要原因,但这些变化目前被归因于钙稳态失调和离子型/代谢型受体变化引起的逐渐突触功能障碍。鉴于海马体在记忆的编码、存储和检索中的关键作用,谷氨酸能网络的主要突触中发生的形态和电生理变化值得特别关注。我们在生理背景下指导您了解海马的解剖结构、电路和功能,并关注衰老和阿尔茨海默病(AD)引起的神经元形态、钙动力学和可塑性的变化。我们提供了谷氨酸能传递的最新知识,并讨论了这些新参与者对干预的影响。在人类中,经常摄入咖啡因(一种腺苷受体阻滞剂)与降低AD风险之间的联系已经得到了很好的证实,而其机制直到现在才被揭示。我们回顾了来自人类和动物模型的令人信服的证据,这些证据表明腺苷A2A受体(A2AR)激增是与年龄相关的突触功能障碍的关键介质。这一机制在患者中的相关性最近以A2AR编码基因与轻度认知障碍和AD患者海马体积(突触损失)的显著关联的形式得到了证实。新的途径表明A2AR在控制mGluR5依赖性NMDAR激活和随后衰老时的Ca2+功能障碍中发挥作用。这种受体的性质使其特别适合长期治疗,作为在衰老和疾病中调节异常mGluR5/NDAR信号的替代品,而不会破坏其关键的组成活性。
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引用次数: 0
Functional and Neuroprotective Role of Striatal Adenosine A2A Receptor Heterotetramers 纹状体腺苷A2A受体异四聚体的功能和神经保护作用
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-09-01 DOI: 10.1089/caff.2019.0008
S. Ferré, F. Ciruela
In the striatum, adenosine A2A receptors (A2AR) are mainly expressed within the soma and dendrites of the striatopallidal neuron. A predominant proportion of these striatal postsynaptic A2AR form part of the macromolecular complexes that include A2AR-dopamine D2 receptor (D2R) heteromers, Golf and Gi/o proteins, and the effector adenylyl cyclase (AC), subtype AC5. The A2AR-D2R heteromers have a tetrameric structure, constituted by A2AR and D2R homomers. By means of reciprocal antagonistic allosteric interactions and antagonistic interactions at the effector level between adenosine and dopamine, the A2AR-D2R heterotetramer-AC5 complex acts an integrative molecular device, which determines a switch between the adenosine-facilitated activation and the dopamine-facilitated inhibition of the striatopallidal neuron. Striatal adenosine also plays an important presynaptic modulatory role, driving the function of corticostriatal terminals. This control is mediated by adenosine A1 receptors (A1R) and A2AR, which establish intermolecular interactions forming A1R-A2AR heterotetramers. Here, we review the functional role of both presynaptic and postsynaptic striatal A2AR heterotetramers as well as their possible neuroprotective role. We hypothesize that alterations in the homomer/heteromer stoichiometry (i.e., increase or decrease in the proportion of A2AR forming homomers or heteromers) are pathogenetically involved in neurological disorders, specifically in Parkinson's disease and restless legs syndrome.
在纹状体中,腺苷A2A受体(A2AR)主要表达于纹状体状神经元的体细胞和树突内。这些纹状体突触后A2AR的主要比例形成了大分子复合物的一部分,包括A2AR-多巴胺D2受体(D2R)异构体、Golf和Gi/o蛋白,以及效应腺苷酸环化酶(AC), AC5亚型。A2AR-D2R异构体具有四聚体结构,由A2AR和D2R异构体组成。A2AR-D2R异四聚体- ac5复合体通过腺苷与多巴胺在效应水平上的拮抗变构相互作用和拮抗相互作用,作为一种整合的分子装置,决定了纹状体神经元在腺苷促进的激活和多巴胺促进的抑制之间的转换。纹状体腺苷也起着重要的突触前调节作用,驱动皮质纹状体末端的功能。这种控制是由腺苷A1受体(A1R)和A2AR介导的,它们建立分子间相互作用,形成A1R-A2AR异源四聚体。在这里,我们回顾了突触前和突触后纹状体A2AR异源四聚体的功能作用及其可能的神经保护作用。我们假设同种异构体化学计量的改变(即A2AR形成同种异构体或异构体比例的增加或减少)在病理上与神经系统疾病有关,特别是帕金森病和不宁腿综合征。
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引用次数: 29
Neurogenetics of the Human Adenosine Receptor Genes: Genetic Structures and Involvement in Brain Diseases 人类腺苷受体基因的神经遗传学:遗传结构与脑疾病的关系
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-09-01 DOI: 10.1089/caff.2019.0011
V. Huin, C. Dhaenens, Mégane Homa, Kevin Carvalho, L. Buée, B. Sablonnière
Adenosine receptors are G-protein-coupled receptors involved in a wide range of physiological and pathological phenomena in most mammalian systems. All four receptors are widely expressed in the ce...
腺苷受体是一种g蛋白偶联受体,在大多数哺乳动物系统中参与广泛的生理和病理现象。这四种受体都广泛表达于…
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引用次数: 10
The Journal of Caffeine and Adenosine Research Welcomes Your Ideas, Research, and Feedback 咖啡因和腺苷研究杂志欢迎您的想法、研究和反馈
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-06-19 DOI: 10.1089/CAFF.2019.29012.KCH
Cloud-HansenKaren
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引用次数: 0
The Beneficial Effects of Postnatal Caffeine on Spatial Learning in Adult Mice 出生后咖啡因对成年小鼠空间学习的有益作用
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-06-19 DOI: 10.1089/CAFF.2018.0021
S. Pratap, XuYing, WangHuamei, H S KumarVasantha
Background: Prenatal caffeine adversely affects learning and memory in adult offspring, whereas its administration to adolescent humans improves consolidation of long-term memory. The effects of po...
背景:产前咖啡因对成年后代的学习和记忆有不利影响,而对青少年服用咖啡因可以改善长期记忆的巩固。的影响……
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引用次数: 2
Caffeine Influences Functional Activity and Gene Expression of Bone Marrow Osteoblastic Cells from Osteoporotic Rats 咖啡因对骨质疏松大鼠骨髓成骨细胞功能活性和基因表达的影响
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-06-19 DOI: 10.1089/CAFF.2019.0002
F. Rodrigo, Vargas SanchezPaula Katherine, SórioAna Luisa Riul, OliveiraCarolina Alves Freiria de, R. Tavares, de Sousa Luiz Gustavo, RosaAdalberto Luiz, SiéssereSelma, B. Fittipaldi
Background: Considering the high consumption of caffeinated beverages and its skeletal effects after onset of osteoporosis, we aimed to evaluate low and moderate in vitro caffeine concentrations in...
背景:考虑到骨质疏松症发作后咖啡因饮料的高消费量及其对骨骼的影响,我们旨在评估体外低浓度和中等浓度的咖啡因。。。
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引用次数: 1
Caffeinated Alcoholic Beverages and Intimate Partner Violence Victimization. 含咖啡因的酒精饮料与亲密伴侣暴力受害。
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-06-01 Epub Date: 2019-06-19 DOI: 10.1089/caff.2018.0018
Cory A Crane, Robert C Schlauch, Kathleen E Miller

Background: Caffeinated alcoholic beverage (CAB) use is associated with general victimization beyond the use of alcohol alone. Materials and Methods: No prior research has evaluated the association between CAB use and intimate partner violence (IPV) victimization. This study evaluated the CAB-IPV victimization relationship using the responses of 100 (40 female) respondents to an online survey. Results: Results of logistic regression analyses indicated that CAB use was associated with IPV physical and sexual victimization after adjusting for demographics and heavy alcohol use. Exploratory analyses detected little evidence of sex differences in the strength of the relationship between CAB use and IPV victimization. Conclusions: The current results provide initial evidence that CAB use may place males and females at greater risk of IPV victimization.

背景:使用含咖啡因的酒精饮料(CAB)与一般受害的相关性超过了单纯使用酒精的相关性。材料与方法:以前没有研究评估过咖啡因酒精饮料的使用与亲密伴侣暴力(IPV)受害之间的关系。本研究通过对 100 名(40 名女性)受访者进行在线调查,评估了 CAB 与 IPV 受害的关系。研究结果逻辑回归分析的结果表明,在对人口统计学和大量饮酒进行调整后,CAB 的使用与 IPV 的身体和性侵害相关。探索性分析几乎没有发现使用 CAB 与 IPV 受害之间的关系存在性别差异。结论:目前的研究结果初步证明,使用 CAB 可能会使男性和女性面临更大的 IPV 受害风险。
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引用次数: 0
Caffeine and Bones: If Less Is Good, More May Not Be Better. 咖啡因和骨骼:少喝好,多喝未必更好
IF 1.7 Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2019-06-01 Epub Date: 2019-06-19 DOI: 10.1089/caff.2019.29011.ah
Luca Antonioli, György Haskó
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Journal of Caffeine and Adenosine Research
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