Title:Xanthine Derivatives as Agents Affecting Non-dopaminergic Neuroprotection in Parkinson’s Disease
Volume: 27
Issue: 12
关键词:
黄嘌呤，咖啡因，帕金森氏病，神经保护，神经退行性疾病，非多巴胺能疗法。
摘要: Parkinson's Disease (PD) is a neurodegenerative and debilitating disease that affects
1% of the elderly population. Patient’s motor disability results in extreme difficulty to
deal with daily activities. Conventional treatment is limited to dopamine replacement therapy,
which fails to delay disease’s progression and is often associated with a number of adverse
reactions. Recent progress in understanding the mechanisms involved in PD has revealed new
molecular targets for therapeutic approaches. Among them, caffeine and xanthine derivatives
are promising drug candidates, because of the possible symptomatic benefits in PD. In fact,
consumption of coffee correlates with a reduced risk of PD. Over the last decades, a lot of efforts
have been made to uncover the therapeutic potential of xanthine structures. The substituted
xanthine molecule is used as a scaffold for the synthesis of new compounds with protective
effects in neurodegenerative diseases, including PD, asthma, cancer and others. The administration
of the xanthines has been proposed as a non-dopaminergic strategy for neuroprotection
in PD and the mechanisms of protection have been associated with antagonism of
adenosine A2A receptors and Monoamine Oxidase type B (MAO-B) inhibition. The current
review summarizes frequently suspected non-dopaminergic neuroprotective mechanisms and
the possible beneficial effects of the xanthine derivatives in PD, along with some synthetic
approaches to produce perspective xanthine derivatives as non-dopaminergic agents in PD
treatment.
