Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany.
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127 Bonn, Germany.
Cells. 2024 Aug 26;13(17):1426. doi: 10.3390/cells13171426.
There is an urgent need for effective disease-modifying therapeutic interventions for Alzheimer's disease (AD)-the most prevalent cause of dementia with a profound socioeconomic burden. Most clinical trials targeting the classical hallmarks of this disease-β-amyloid plaques and neurofibrillary tangles-failed, showed discrete clinical effects, or were accompanied by concerning side effects. There has been an ongoing search for novel therapeutic targets. Neuroinflammation, now widely recognized as a hallmark of all neurodegenerative diseases, has been proven to be a major contributor to AD pathology. Here, we summarize the role of neuroinflammation in the pathogenesis and progression of AD and discuss potential targets such as microglia, TREM2, the complement system, inflammasomes, and cytosolic DNA sensors. We also present an overview of ongoing studies targeting specific innate immune system components, highlighting the progress in this field of drug research while bringing attention to the delicate nature of innate immune modulations in AD.
目前，对于阿尔茨海默病（AD）这种最常见的痴呆症病因，我们急需有效的疾病修饰治疗干预措施，该病给社会经济带来了巨大负担。大多数针对该疾病的经典特征（β-淀粉样斑块和神经原纤维缠结）的临床试验都失败了，仅显示出离散的临床效果，或者伴有令人担忧的副作用。目前，人们一直在寻找新的治疗靶点。神经炎症，现在被广泛认为是所有神经退行性疾病的标志，已被证明是 AD 病理的主要原因之一。在这里，我们总结了神经炎症在 AD 发病机制和进展中的作用，并讨论了一些潜在的靶点，如小胶质细胞、TREM2、补体系统、炎性体和胞质 DNA 传感器。我们还概述了针对特定固有免疫系统成分的正在进行的研究，强调了药物研究领域的进展，同时也注意到 AD 中固有免疫调节的微妙性质。
