Iliyasu Musa O, Musa Sunday A, Oladele Sunday B, Iliya Abdullahi I
Department of Anatomy, Kogi State University, Anyigba, Nigeria.
Department of Human Anatomy, Ahmadu Bello University, Zaria, Nigeria.
Front Neurosci. 2023 Apr 11;17:1081938. doi: 10.3389/fnins.2023.1081938. eCollection 2023.
Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by tau pathology and accumulations of neurofibrillary tangles (NFTs) along with amyloid-beta (Aβ). It has been associated with neuronal damage, synaptic dysfunction, and cognitive deficits. The current review explained the molecular mechanisms behind the implications of Aβ aggregation in AD multiple events. Beta (β) and gamma (γ) secretases hydrolyzed amyloid precursor protein (APP) to produce Aβ, which then clumps together to form Aβ fibrils. The fibrils increase oxidative stress, inflammatory cascade, and caspase activation to cause hyperphosphorylation of tau protein into neurofibrillary tangles (NFTs), which ultimately lead to neuronal damage. Acetylcholine (Ach) degradation is accelerated by upstream regulation of the acetylcholinesterase (AChE) enzyme, which leads to a deficiency in neurotransmitters and cognitive impairment. There are presently no efficient or disease-modifying medications for AD. It is necessary to advance AD research to suggest novel compounds for treatment and prevention. Prospectively, it might be reasonable to conduct clinical trials with unclean medicines that have a range of effects, including anti-amyloid and anti-tau, neurotransmitter modulation, anti-neuroinflammatory, neuroprotective, and cognitive enhancement.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为tau病理变化以及神经原纤维缠结（NFTs）与β淀粉样蛋白（Aβ）的积聚。它与神经元损伤、突触功能障碍和认知缺陷有关。本综述解释了Aβ聚集在AD多个事件中的潜在分子机制。β和γ分泌酶水解淀粉样前体蛋白（APP）以产生Aβ，然后Aβ聚集在一起形成Aβ纤维。这些纤维会增加氧化应激、炎症级联反应和半胱天冬酶激活，从而导致tau蛋白过度磷酸化形成神经原纤维缠结（NFTs），最终导致神经元损伤。乙酰胆碱酯酶（AChE）酶的上游调节加速了乙酰胆碱（Ach）的降解，导致神经递质缺乏和认知障碍。目前尚无治疗AD的有效或疾病修饰药物。推进AD研究以提出用于治疗和预防的新型化合物很有必要。前瞻性地，对具有一系列作用（包括抗淀粉样蛋白和抗tau、神经递质调节、抗神经炎症、神经保护和认知增强）的非洁净药物进行临床试验可能是合理的。
