Sharkus Robert, Thakkar Richa, Kolson Dennis L, Constantinescu Cris S
Department of Neurology, Cooper Neurological Institute, Cherry Hill, NJ 08002, USA.
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Biomedicines. 2023 May 8;11(5):1387. doi: 10.3390/biomedicines11051387.
Alzheimer's Disease (AD) is a debilitating disease that leads to severe cognitive impairment and functional decline. The role of tau hyperphosphorylation and amyloid plaque deposition in the pathophysiology of AD has been well described; however, neuroinflammation and oxidative stress related to sustained microglial activation is thought to play a significant role in the disease process as well. NRF-2 has been identified in modulating the effects of inflammation and oxidative stress in AD. Activation of NRF-2 leads to an increased production of antioxidant enzymes, including heme oxygenase, which has been shown to have protective effects in neurodegenerative disorders such as AD. Dimethyl fumarate and diroximel fumarate (DMF) have been approved for the use in relapsing-remitting multiple sclerosis. Research indicates that they can modulate the effects of neuroinflammation and oxidative stress through the NRF-2 pathway, and as such, could serve as a potential therapeutic option in AD. We propose a clinical trial design that could be used to assess DMF as a treatment option for AD.
阿尔茨海默病（AD）是一种使人衰弱的疾病，会导致严重的认知障碍和功能衰退。tau蛋白过度磷酸化和淀粉样斑块沉积在AD病理生理学中的作用已得到充分描述；然而，与小胶质细胞持续激活相关的神经炎症和氧化应激也被认为在疾病过程中起重要作用。已确定核因子E2相关因子2（NRF-2）在调节AD中的炎症和氧化应激作用。NRF-2的激活会导致抗氧化酶产量增加，包括血红素加氧酶，已证明其在AD等神经退行性疾病中具有保护作用。富马酸二甲酯和二甲基富马酸罗克昔（DMF）已被批准用于复发缓解型多发性硬化症。研究表明，它们可以通过NRF-2途径调节神经炎症和氧化应激的作用，因此，有可能成为AD的一种潜在治疗选择。我们提出了一种临床试验设计，可用于评估DMF作为AD治疗选择的效果。
