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Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies.

Abstract

Neurodegenerative disorders are some of the most feared illnesses in modern society, with no effective treatments to slow or halt this neurodegeneration. Several decades after the earliest attempt to treat Parkinson's disease using caffeine, tremendous amounts of information regarding the potential beneficial effect of caffeine as well as adenosine drugs on major neurodegenerative disorders have accumulated. In the first part of this review, we provide general background on the adenosine receptor signaling systems by which caffeine and methylxanthine modulate brain activity and their role in relationship to the development and treatment of neurodegenerative disorders. The demonstration of close interaction between adenosine receptor and other G protein coupled receptors and accessory proteins might offer distinct pharmacological properties from adenosine receptor monomers. This is followed by an outline of the major mechanism underlying neuroprotection against neurodegeneration offered by caffeine and adenosine receptor agents. In the second part, we discuss the current understanding of caffeine/methylxantheine and its major target adenosine receptors in development of individual neurodegenerative disorders, including stroke, traumatic brain injury Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple sclerosis. The exciting findings to date include the specific in vivo functions of adenosine receptors revealed by genetic mouse models, the demonstration of a broad spectrum of neuroprotection by chronic treatment of caffeine and adenosine receptor ligands in animal models of neurodegenerative disorders, the encouraging development of several A(2A) receptor selective antagonists which are now in advanced clinical phase III trials for Parkinson's disease. Importantly, increasing body of the human and experimental studies reveals encouraging evidence that regular human consumption of caffeine in fact may have several beneficial effects on neurodegenerative disorders, from motor stimulation to cognitive enhancement to potential neuroprotection. Thus, with regard to neurodegenerative disorders, these potential benefits of methylxanthines, caffeine in particular, strongly argue against the common practice by clinicians to discourage regular human consumption of caffeine in aging populations.

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  • Authors+Show Affiliations

    ,

    Department of Neurology, Boston University School of Medicine, Boston, MA, USA. chenjf@bu.edu

    Source

    MeSH

    Alzheimer Disease
    Animals
    Brain Injuries
    Caffeine
    Humans
    Huntington Disease
    Neurodegenerative Diseases
    Neuroprotective Agents
    Receptors, Purinergic P1
    Stroke
    Xanthines

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    20859800

    Citation

    Chen, Jiang-Fan, and Yijuang Chern. "Impacts of Methylxanthines and Adenosine Receptors On Neurodegeneration: Human and Experimental Studies." Handbook of Experimental Pharmacology, 2011, pp. 267-310.
    Chen JF, Chern Y. Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. Handb Exp Pharmacol. 2011.
    Chen, J. F., & Chern, Y. (2011). Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. Handbook of Experimental Pharmacology, (200), pp. 267-310. doi:10.1007/978-3-642-13443-2_10.
    Chen JF, Chern Y. Impacts of Methylxanthines and Adenosine Receptors On Neurodegeneration: Human and Experimental Studies. Handb Exp Pharmacol. 2011;(200)267-310. PubMed PMID: 20859800.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. AU - Chen,Jiang-Fan, AU - Chern,Yijuang, PY - 2010/9/23/entrez PY - 2010/9/23/pubmed PY - 2011/1/5/medline SP - 267 EP - 310 JF - Handbook of experimental pharmacology JO - Handb Exp Pharmacol IS - 200 N2 - Neurodegenerative disorders are some of the most feared illnesses in modern society, with no effective treatments to slow or halt this neurodegeneration. Several decades after the earliest attempt to treat Parkinson's disease using caffeine, tremendous amounts of information regarding the potential beneficial effect of caffeine as well as adenosine drugs on major neurodegenerative disorders have accumulated. In the first part of this review, we provide general background on the adenosine receptor signaling systems by which caffeine and methylxanthine modulate brain activity and their role in relationship to the development and treatment of neurodegenerative disorders. The demonstration of close interaction between adenosine receptor and other G protein coupled receptors and accessory proteins might offer distinct pharmacological properties from adenosine receptor monomers. This is followed by an outline of the major mechanism underlying neuroprotection against neurodegeneration offered by caffeine and adenosine receptor agents. In the second part, we discuss the current understanding of caffeine/methylxantheine and its major target adenosine receptors in development of individual neurodegenerative disorders, including stroke, traumatic brain injury Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple sclerosis. The exciting findings to date include the specific in vivo functions of adenosine receptors revealed by genetic mouse models, the demonstration of a broad spectrum of neuroprotection by chronic treatment of caffeine and adenosine receptor ligands in animal models of neurodegenerative disorders, the encouraging development of several A(2A) receptor selective antagonists which are now in advanced clinical phase III trials for Parkinson's disease. Importantly, increasing body of the human and experimental studies reveals encouraging evidence that regular human consumption of caffeine in fact may have several beneficial effects on neurodegenerative disorders, from motor stimulation to cognitive enhancement to potential neuroprotection. Thus, with regard to neurodegenerative disorders, these potential benefits of methylxanthines, caffeine in particular, strongly argue against the common practice by clinicians to discourage regular human consumption of caffeine in aging populations. SN - 0171-2004 UR - https://www.unboundmedicine.com/medline/citation/20859800/Impacts_of_methylxanthines_and_adenosine_receptors_on_neurodegeneration:_human_and_experimental_studies_ L2 - https://dx.doi.org/10.1007/978-3-642-13443-2_10 DB - PRIME DP - Unbound Medicine ER -