Department of Medical Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
Acibadem Labmed Clinical Laboratories, R&D Center, Istanbul, Turkey.
Curr Med Chem. 2021;28(17):3449-3473. doi: 10.2174/0929867327999201116193126.
Alzheimer's disease is one of the leading health problems characterized by the accumulation of Aβ and hyperphosphorylated tau that account for the senile plaque formations causing extensive cognitive decline. Many of the clinical diagnoses of Alzheimer's disease are made in the late stages, when the pathological changes have already progressed.
The objective of this study is to evaluate the promising therapeutic effects of a natural compound, lycoramine, which has been shown to have therapeutic potential in several studies and to understand its mechanism of action on the molecular level via differential protein expression analyses.
Lycoramine and galantamine, an FDA approved drug used in the treatment of mild to moderate AD, were administered to 12 month-old 5xFAD mice. Effects of the compounds were investigated by Morris water maze, immunohistochemistry and label- free differential protein expression analyses.
Here we demonstrated the reversal of cognitive decline via behavioral testing and the clearance of Aβ plaques. Proteomics analysis provided in-depth information on the statistically significant protein perturbations in the cortex, hippocampus and cerebellum sections to hypothesize the possible clearance mechanisms of the plaque formation and the molecular mechanism of the reversal of cognitive decline in a transgenic mouse model. Bioinformatics analyses showed altered molecular pathways that can be linked with the reversal of cognitive decline observed after lycoramine administration but not with galantamine.
Lycoramine shows therapeutic potential to halt and reverse cognitive decline at the late stages of disease progression, and holds great promise for the treatment of Alzheimer's disease.
阿尔茨海默病是最主要的健康问题之一，其特征是 Aβ 和过度磷酸化的 tau 的积累，这两者导致了老年斑的形成，从而造成广泛的认知能力下降。许多阿尔茨海默病的临床诊断都是在疾病进展的后期做出的，此时病理变化已经进展。
本研究的目的是评估一种天然化合物石蒜堿的有前途的治疗效果，该化合物在几项研究中显示出治疗潜力，并通过差异蛋白质表达分析了解其在分子水平上的作用机制。
给 12 月龄的 5xFAD 小鼠施用石蒜堿和加兰他敏，一种用于治疗轻度至中度 AD 的 FDA 批准药物。通过 Morris 水迷宫、免疫组织化学和无标记差异蛋白质表达分析来研究化合物的作用。
我们通过行为测试和 Aβ 斑块的清除证明了认知能力下降的逆转。蛋白质组学分析提供了皮质、海马体和小脑切片中统计学上显著的蛋白质扰动的深入信息，以假设斑块形成的可能清除机制和转基因小鼠模型中认知能力下降逆转的分子机制。生物信息学分析显示，改变的分子途径可以与石蒜堿给药后观察到的认知能力下降的逆转相关联，但与加兰他敏无关。
石蒜堿具有在疾病进展后期阻止和逆转认知能力下降的治疗潜力，为阿尔茨海默病的治疗提供了很大的希望。
