Munafò Antonio, Burgaletto Chiara, Di Benedetto Giulia, Di Mauro Marco, Di Mauro Rosaria, Bernardini Renato, Cantarella Giuseppina
Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy.
Unit of Clinical Toxicology, University Hospital, University of Catania, Catania, Italy.
Front Neurosci. 2020 Dec 4;14:614643. doi: 10.3389/fnins.2020.614643. eCollection 2020.
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid β plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain's pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.
阿尔茨海默病(AD)是最常见的与年龄相关的神经退行性疾病,其特征为认知功能下降以及大脑中存在淀粉样β斑块和神经原纤维缠结。尽管在理解其病理生理机制方面取得了最新进展,但迄今为止,尚无改变疾病进程的治疗选择来减缓或阻止AD中神经退行性过程的进展。目前的药物治疗仅能暂时减轻症状的严重程度,总体改善程度不大或没有改善。新出现的证据支持这样一种观点,即AD受到免疫系统抑制大脑病理能力受损的影响。深入了解神经与免疫系统之间的关系可能为开发有效且安全的AD治疗药物提供一个新领域。考虑到炎症/免疫途径在AD中的关键作用,在此我们通过药物重新定位方法讨论正在临床前研究或正在进行的临床试验中使用的免疫肿瘤学、免疫调节和抗TNF-α药物的现状。