Background: Neuronal Microtubule (MT) tau protein, providing cytoskeleton to neuronal cells, plays a vital role, including maintenance of cell shape, intracellular transport, and cell division. Tau hyperphosphorylation mediated MT destabilization results in axonopathy, additionally neurotransmitter deficit and ultimately causing Alzheimer's disease. Pre-clinically, streptozotocin (3mg/kg, 10μl/ unilateral, ICV) stereotaxically mimics the behavioral and neurochemical alterations similar to Alzheimer's tau pathology resulting in MT assembly defects further lead to neuropathological cascades.

Objective: Clinically approved medications such as Donepezil (DNP), rivastigmine, and Memantine (MEM) are responsible for symptomatic care only, but there is no specific pharmacological intervention that directly interacts with the neuronal microtubule destabilization.

Methods: The current study focused on the involvement of anti-cancer agent microtubule stabilizer cabazitaxel at a low dose (0.5 and 2 mg/kg) alone and in combination with standard drugs DNP (5 mg/kg), MEM (10 mg/kg) and microtubule stabilizer Epothilone D (EpoD) (3 mg/kg) in the prevention of intracerebroventricular streptozotocin (ICV-STZ) intoxicated microtubule-associated tau protein hyperphosphorylation.

Results: Chronic treatment of CBZ at a low dose alone and in combination with standard drugs showing no side effect and significantly improve the cognitive impairment, neurochemical alterations along with reducing the level of hyperphosphorylated tau by preventing the breakdown of the neuronal cytoskeleton, respectively.

Conclusion: The above findings suggested that CBZ at low dose show neuroprotective effects against ICV-STZ induced microtubule-associated tau protein hyperphosphorylation in rats and may be an effective agent for the preventive treatment of AD.

背景：神经元微管 (MT) tau 蛋白为神经元细胞提供细胞骨架，起着至关重要的作用，包括维持细胞形状、细胞内运输和细胞分裂。Tau 过度磷酸化介导的 MT 不稳定导致轴突病、神经递质缺陷并最终导致阿尔茨海默病。临床前，链脲佐菌素（3mg/kg，10μl/单侧，ICV）立体模拟类似于阿尔茨海默氏 tau 病理学的行为和神经化学改变，导致 MT 组装缺陷，进一步导致神经病理学级联反应。

目的：临床批准的药物如多奈哌齐 (DNP)、利凡斯的明和美金刚 (MEM) 仅负责对症治疗，但没有直接与神经元微管不稳定相互作用的特定药理学干预。

方法：目前的研究重点是抗癌剂微管稳定剂卡巴他赛在低剂量（0.5 和 2 毫克/公斤）下单独和与标准药物 DNP（5 毫克/公斤）、MEM（10 毫克/公斤) 和微管稳定剂埃坡霉素 D (EpoD) (3 mg/kg) 可预防脑室内链脲佐菌素 (ICV-STZ) 中毒的微管相关 tau 蛋白过度磷酸化。

结果：CBZ 单独以低剂量和与标准药物联合的慢性治疗显示无副作用，并通过防止神经元细胞骨架的分解分别显着改善认知障碍、神经化学改变以及降低过度磷酸化 tau 的水平。

结论：上述研究结果表明，低剂量 CBZ 对 ICV-STZ 诱导的大鼠微管相关 tau 蛋白过度磷酸化具有神经保护作用，可能是预防 AD 的有效药物。