Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
C.A.R., Cambridge, UK.
Neurosci Biobehav Rev. 2021 Jun;125:244-263. doi: 10.1016/j.neubiorev.2021.02.037. Epub 2021 Feb 28.
Lowered high-density lipoprotein (HDL) cholesterol has been reported in major depressive disorder, bipolar disorder, first episode of psychosis, and schizophrenia. HDL, its major apolipoprotein component, ApoA1, and the antioxidant enzyme paraoxonase (PON)1 (which is normally bound to ApoA1) all have anti-atherogenic, antioxidant, anti-inflammatory, and immunomodulatory roles, which are discussed in this paper. The paper details the pathways mediating the anti-inflammatory effects of HDL, ApoA1 and PON1 and describes the mechanisms leading to compromised HDL and PON1 levels and function in an environment of chronic inflammation. The molecular mechanisms by which changes in HDL, ApoA1 and PON1 might contribute to the pathophysiology of the neuroprogressive disorders are explained. Moreover, the anti-inflammatory actions of ApoM-mediated sphingosine 1-phosphate (S1P) signalling are reviewed as well as the deleterious effects of chronic inflammation and oxidative stress on ApoM/S1P signalling. Finally, therapeutic interventions specifically aimed at improving the levels and function of HDL and PON1 while reducing levels of inflammation and oxidative stress are considered. These include the so-called Mediterranean diet, extra virgin olive oil, polyphenols, flavonoids, isoflavones, pomegranate juice, melatonin and the Mediterranean diet combined with the ketogenic diet.
已有研究报道，在重度抑郁症、双相情感障碍、首发精神病和精神分裂症中，高密度脂蛋白（HDL）胆固醇水平降低。HDL、其主要载脂蛋白成分载脂蛋白 A1（ApoA1）和抗氧化酶对氧磷酶 1（PON1）（通常与 ApoA1 结合）均具有抗动脉粥样硬化、抗氧化、抗炎和免疫调节作用，本文对此进行了讨论。本文详细介绍了介导 HDL、ApoA1 和 PON1 抗炎作用的途径，并描述了在慢性炎症环境中导致 HDL 和 PON1 水平和功能受损的机制。解释了 HDL、ApoA1 和 PON1 变化如何导致神经进行性疾病病理生理学的分子机制。此外，还回顾了 ApoM 介导的鞘氨醇 1-磷酸（S1P）信号转导的抗炎作用以及慢性炎症和氧化应激对 ApoM/S1P 信号转导的有害影响。最后，考虑了专门旨在提高 HDL 和 PON1 水平和功能，同时降低炎症和氧化应激水平的治疗干预措施。这些措施包括所谓的地中海饮食、特级初榨橄榄油、多酚、类黄酮、异黄酮、石榴汁、褪黑素和地中海饮食与生酮饮食相结合。
