Department of Anatomy and Neurobiology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA.
Government College of Pharmacy, Shimla, Himachal Pradesh, India.
Chem Biol Drug Des. 2023 Dec;102(6):1592-1603. doi: 10.1111/cbdd.14337. Epub 2023 Sep 4.
Alzheimer's disease (AD) is a chronic age-related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability of an individual. The exact pathophysiology of AD is not fully understood. However low level of the neurotransmitter named acetylcholine (ACh), aggregation of Aβ peptide into toxic Aβ plaque, hyperphosphorylation of tau, bio-metal imbalance, and oxidative stress are the main hallmarks of this disease. Due to the complex pathophysiology of AD, no specific treatment is available in the market, and treatment is only limited to the symptomatic relief. So, there is an urgent need for the development of new drug candidate, which can have disease-modifying effect and improve learning and memory in AD patient. Therefore, berberine-based multifunction compounds with potential cholinesterase inhibitory properties were reviewed in this article. Structure-activity relationship (SAR) and biological activity provide highlights on the new derivatives used for the management of AD.
阿尔茨海默病(AD)是一种慢性与年龄相关的神经退行性脑疾病,其特征是个体的记忆受损,思维能力恶化。AD 的确切病理生理学尚未完全了解。然而,神经递质乙酰胆碱(ACh)水平低、Aβ肽聚集成有毒的 Aβ斑块、tau 过度磷酸化、生物金属失衡和氧化应激是这种疾病的主要标志。由于 AD 的病理生理学复杂,市场上没有有效的特定治疗方法,治疗仅限于对症缓解。因此,迫切需要开发新的候选药物,这种药物具有疾病修饰作用,并能改善 AD 患者的学习和记忆。因此,本文综述了具有潜在胆碱酯酶抑制特性的基于小檗碱的多功能化合物。结构-活性关系(SAR)和生物学活性突出了用于 AD 管理的新衍生物。