MTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, Hungary.
Department of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Int J Mol Sci. 2020 Mar 31;21(7):2431. doi: 10.3390/ijms21072431.
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases (NDs), presenting a broad range of symptoms from motor dysfunctions to psychobehavioral manifestations. A common clinical course is the proteinopathy-induced neural dysfunction leading to anatomically corresponding neuropathies. However, current diagnostic criteria based on pathology and symptomatology are of little value for the sake of disease prevention and drug development. Overviewing the pathomechanism of NDs, this review incorporates systematic reviews on inflammatory cytokines and tryptophan metabolites kynurenines (KYNs) of human samples, to present an inferential method to explore potential links behind NDs. The results revealed increases of pro-inflammatory cytokines and neurotoxic KYNs in NDs, increases of anti-inflammatory cytokines in AD, PD, Huntington's disease (HD), Creutzfeldt-Jakob disease, and human immunodeficiency virus (HIV)-associated neurocognitive disorders, and decreases of neuromodulatory KYNs in AD, PD, and HD. The results reinforced a strong link between inflammation and neurotoxic KYNs, confirmed activation of adaptive immune response, and suggested a possible role in the decrease of neuromodulatory KYNs, all of which may contribute to the development of chronic low grade inflammation. Commonalities of multifactorial NDs were discussed to present a current limit of diagnostic criteria, a need for preclinical biomarkers, and an approach to search the initiation factors of NDs.
阿尔茨海默病（AD）和帕金森病（PD）是最常见的神经退行性疾病（NDs），表现出广泛的症状，从运动功能障碍到精神行为表现。常见的临床过程是蛋白病引起的神经功能障碍导致解剖学上相应的神经病变。然而，目前基于病理学和症状学的诊断标准对于疾病预防和药物开发几乎没有价值。本文概述了 NDs 的发病机制，纳入了人类样本中炎症细胞因子和色氨酸代谢物犬尿氨酸（KYNs）的系统评价，提出了一种推断方法来探索 NDs 背后的潜在联系。结果表明，在 NDs 中促炎细胞因子和神经毒性 KYNs 增加，AD、PD、亨廷顿病（HD）、克雅氏病和人类免疫缺陷病毒（HIV）相关神经认知障碍中抗炎细胞因子增加，AD、PD 和 HD 中神经调节 KYNs 减少。这些结果强化了炎症与神经毒性 KYNs 之间的紧密联系，证实了适应性免疫反应的激活，并提示了神经调节 KYNs 减少的可能作用，所有这些都可能有助于慢性低度炎症的发展。讨论了多因素 NDs 的共性，以提出当前诊断标准的局限性、临床前生物标志物的需求以及寻找 NDs 起始因素的方法。
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