Uddin Md Sahab, Kabir Md Tanvir, Rahman Md Motiar, Mathew Bijo, Shah Muhammad Ajmal, Ashraf Ghulam Md
Department of Pharmacy, Southeast University, Dhaka, Bangladesh.
Pharmakon Neuroscience Research Network, Dhaka, Bangladesh.
J Pharm Pharmacol. 2020 Aug;72(8):1001-1012. doi: 10.1111/jphp.13244. Epub 2020 Mar 9.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and a well-recognized cause of dementia with ageing. In this review, we have represented the ChE and MAO inhibitory potential of TV 3326 against AD based on current scientific evidence.
The aetiology of AD is quite complex and not completely understood. However, it has been observed that AD involves the deposition of abnormal amyloid beta (Aβ), along with hyperphosphorylation of tau, oxidative stress, low acetylcholine (ACh) level and biometal dyshomeostasis. Due to the complex nature of AD aetiology, active research is required in the areas of development of multitarget drugs with 2 or more complementary biological functions, as they might represent significant progress in the AD treatment. Interestingly, it has been found that TV 3326 (i.e. ladostigil) is regarded as a novel therapeutic agent since it has the potential to cause inhibition of monoamine oxidase (MAO) A and B, and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain. Furthermore, it has the capacity to reverse memory impairments, which further suggests the ability of this drug to elevate cholinergic activity in the brain.
TV 3326 can avert oxidative-nitrative stress and gliosis. It has also been confirmed that TV 3326 contains neuroprotective and anti-apoptotic properties. Therefore, this distinctive combined inhibition of ChE and MAO along with its neuroprotective property makes TV 3326 a useful drug in the treatment of AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病之一，也是公认的与衰老相关的痴呆病因。在本综述中，我们基于当前科学证据阐述了TV 3326对AD的胆碱酯酶（ChE）和单胺氧化酶（MAO）抑制潜力。
AD的病因相当复杂，尚未完全明确。然而，据观察，AD涉及异常淀粉样β蛋白（Aβ）的沉积，以及tau蛋白的过度磷酸化、氧化应激、乙酰胆碱（ACh）水平降低和生物金属稳态失衡。由于AD病因的复杂性，需要在开发具有两种或更多互补生物学功能的多靶点药物领域进行积极研究，因为它们可能代表AD治疗的重大进展。有趣的是，已发现TV 3326（即拉多替吉）被视为一种新型治疗药物，因为它有可能抑制大脑中的单胺氧化酶（MAO）A和B、乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）。此外，它有能力逆转记忆障碍，这进一步表明该药物能够提高大脑中的胆碱能活性。
TV 3326可以避免氧化-硝化应激和胶质细胞增生。还证实TV 3326具有神经保护和抗凋亡特性。因此，这种对ChE和MAO的独特联合抑制及其神经保护特性使TV 3326成为治疗AD的一种有用药物。
