Mogavero Maria P, Silvani Alessandro, DelRosso Lourdes M, Salemi Michele, Ferri Raffaele
Istituti Clinici Scientifici Maugeri, IRCCS, Scientific Institute of Pavia, 27100 Pavia, Italy.
Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy.
Cancers (Basel). 2021 May 26;13(11):2612. doi: 10.3390/cancers13112612.
Conditions such as Alzheimer's (AD) and Parkinson's diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.
阿尔茨海默病（AD）和帕金森病（PD）等病症在癌症幸存者中不太常见，总体而言，这些神经退行性疾病患者患癌症的几率也较低。这似乎表明，易患一种疾病的倾向可能会降低患另一种疾病的风险。除了流行病学数据外，还有证据表明存在复杂的生物学联系，癌症和神经退行性疾病中的基因、蛋白质和信号通路往往表现出相反的失调。在这篇叙述性综述中，我们重点关注食欲素信号传导可能发挥的作用，1型发作性睡病患者以及AD和PD患者的食欲素信号传导发生了改变，在小鼠模型中，食欲素信号传导与脑β-淀粉样蛋白水平和炎症有关，在细胞系中与癌症有关。综合这些证据表明，癌症和神经退行性疾病之间可能存在反向共病情况，食欲素在其中发挥了作用。这些考虑因素提示了食欲素调节在发作性睡病、神经退行性疾病和癌症等多种病症中的治疗潜力。
