Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy -
Plants for Human Health Institute, Department of Animal Sciences, NC Research Campus, North Carolina State University, Kannapolis, NC, USA.
Minerva Med. 2019 Jun;110(3):238-250. doi: 10.23736/S0026-4806.18.05875-5. Epub 2018 Oct 11.
At present, the etiopathogenesis of Alzheimer's disease (AD), the most common form of dementia, remains far to be fully deciphered. In the recent years, also the centrality of amyloid-β peptide in the pathogenesis of the neurodegenerative disease has been questioned and other hypotheses have been advanced. Notably, a common denominator of many of these theoretical models is represented by oxidative stress, which is widely proposed to play a role in the disease initiation and/or progression. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that endows its carrier with multiple biological functions, including the ability to contrast oxidative damage to lipid components of lipoproteins and cells and protect from toxicity of specific organophosphorus pesticides. The peculiar multi-functionality nature of PON1 might be the key for explaining the vast epidemiological data showing a close association between low serum PON1 activity and risk of several diseases, including cardiovascular and neurodegenerative diseases, in particular AD. In this review, we discuss the possible link between PON1 with AD pathogenesis and we hypothesize eventual mechanistic pathways that could account from epidemiological observations. We also highlight the methodological issue limitation in PON1 studies that still impede to give a definitive and certain picture of its effective biological impact on human health including AD.
目前，阿尔茨海默病（AD）——最常见的痴呆症形式——的发病机制仍然远未被完全阐明。近年来，淀粉样β肽在神经退行性疾病发病机制中的中心地位也受到质疑，提出了其他假说。值得注意的是，这些理论模型中的许多共同因素是氧化应激，它被广泛认为在疾病的发生和/或进展中起作用。对氧磷酶 1（PON1）是一种高密度脂蛋白（HDL）相关的酶，它赋予其载体多种生物学功能，包括抵抗脂蛋白和细胞脂质成分氧化损伤的能力，并能抵御特定有机磷农药的毒性。PON1 的特殊多功能性质可能是解释大量流行病学数据的关键，这些数据表明，血清 PON1 活性低与多种疾病（包括心血管疾病和神经退行性疾病，特别是 AD）的风险密切相关。在这篇综述中，我们讨论了 PON1 与 AD 发病机制之间的可能联系，并假设了可能的机制途径，可以从流行病学观察结果来解释。我们还强调了 PON1 研究中的方法学问题限制，这些问题仍然阻碍了对其对人类健康（包括 AD）的有效生物学影响的明确和确定的描述。
