Ambreen Subiya, Fatima Naurin, Umar Mohammad, Shaququzzaman Mohd, Alam Mohammad Mumtaz, Ali Ruhi
Department of Pharmaceutical Chemistry, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, 110017, India.
Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India.
Curr Top Med Chem. 2023 Oct 5. doi: 10.2174/0115680266274924231002110733.
Alzheimer's disease (AD) has been recognized as the most important cause of dementia, which is estimated to contribute more than 2 trillion USD in medical costs. AD patients encounter progressive neurodegenerative dementia associated with behavioural, linguistic, and visuospatial deficits. Although studies on the discovery of amyloid β (Aβ) and tau (the essential elements of plaques and tangles in AD) have shed light on the molecular pathological processes of AD, the exact cause of the condition is still largely unknown. The involvement of various proteins, such as amyloid-β, prion protein, tau, and α-synuclein has been linked to AD pathogenesis. The current AD treatments are mainly based on symptomatic management and restoration of neurotransmitters' balance. There is a significant need to develop medications that can alter the underlying disease process and prevent its progression. The present manuscript provides a review of various hypotheses that have been proposed for AD pathogenesis. The manuscript has also explored the development of novel anti-AD drugs based on various pathogenic pathways, which are recently under various clinical trial phases.
阿尔茨海默病(AD)已被公认为痴呆症的最重要病因,据估计其医疗费用超过2万亿美元。AD患者会出现与行为、语言和视觉空间缺陷相关的进行性神经退行性痴呆。尽管对淀粉样蛋白β(Aβ)和tau(AD中斑块和缠结的关键成分)的研究为AD的分子病理过程提供了线索,但该病的确切病因在很大程度上仍不清楚。各种蛋白质的参与,如淀粉样蛋白-β、朊病毒蛋白、tau蛋白和α-突触核蛋白,都与AD的发病机制有关。目前AD的治疗主要基于对症治疗和恢复神经递质平衡。迫切需要开发能够改变潜在疾病进程并预防其进展的药物。本手稿对已提出的AD发病机制的各种假说进行了综述。该手稿还探讨了基于各种致病途径的新型抗AD药物的开发情况,这些药物目前正处于不同的临床试验阶段。