Altay Ozlem, Yang Hong, Yildirim Serkan, Bayram Cemil, Bolat Ismail, Oner Sena, Tozlu Ozlem Ozdemir, Arslan Mehmet Enes, Hacimuftuoglu Ahmet, Shoaie Saeed, Zhang Cheng, Borén Jan, Uhlén Mathias, Turkez Hasan, Mardinoglu Adil
Science for Life Laboratory, KTH-Royal Institute of Technology, 171 65 Stockholm, Sweden.
Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum 25240, Turkey.
Biomedicines. 2024 Apr 22;12(4):927. doi: 10.3390/biomedicines12040927.
Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD. CMAs include substances such as the glutathione precursors (L-serine and N-acetyl cysteine), the NAD+ precursor (nicotinamide riboside), and L-carnitine tartrate.
Here, we tested the effect of two different formulations, including CMA1 (nicotinamide riboside, L-serine, N-acetyl cysteine, L-carnitine tartrate), and CMA2 (nicotinamide, L-serine, N-acetyl cysteine, L-carnitine tartrate), as well as their individual components, on the animal models of AD and PD. We assessed the brain and liver tissues for pathological changes and immunohistochemical markers. Additionally, in the case of PD, we performed behavioral tests and measured responses to apomorphine-induced rotations.
Histological analysis showed that the administration of both CMA1 and CMA2 formulations led to improvements in hyperemia, degeneration, and necrosis in neurons for both AD and PD models. Moreover, the administration of CMA2 showed a superior effect compared to CMA1. This was further corroborated by immunohistochemical data, which indicated a reduction in immunoreactivity in the neurons. Additionally, notable metabolic enhancements in liver tissues were observed using both formulations. In PD rat models, the administration of both formulations positively influenced the behavioral functions of the animals.
Our findings suggest that the administration of both CMA1 and CMA2 markedly enhanced metabolic and behavioral outcomes, aligning with neuro-histological observations. These findings underscore the promise of CMA2 administration as an effective therapeutic strategy for enhancing metabolic parameters and cognitive function in AD and PD patients.
线粒体功能障碍和代谢异常被认为是帕金森病（PD）和阿尔茨海默病（AD）等神经退行性疾病发病的重要因素。我们的研究表明，联合使用代谢激活剂（CMA）可能减轻代谢功能障碍并刺激线粒体代谢。因此，使用CMA可能是减缓或阻止PD和AD进展的有效治疗策略。CMA包括谷胱甘肽前体（L-丝氨酸和N-乙酰半胱氨酸）、NAD+前体（烟酰胺核糖）和L-酒石酸肉碱等物质。
在此，我们测试了两种不同配方，即CMA1（烟酰胺核糖、L-丝氨酸、N-乙酰半胱氨酸、L-酒石酸肉碱）和CMA2（烟酰胺、L-丝氨酸、N-乙酰半胱氨酸、L-酒石酸肉碱）及其各个成分对AD和PD动物模型的影响。我们评估了脑和肝组织的病理变化和免疫组化标记物。此外，对于PD，我们进行了行为测试并测量了对阿扑吗啡诱导旋转的反应。
组织学分析表明，给予CMA1和CMA2配方均能改善AD和PD模型神经元的充血、变性和坏死。此外，与CMA1相比，给予CMA2显示出更好的效果。免疫组化数据进一步证实了这一点，该数据表明神经元中的免疫反应性降低。此外，使用这两种配方均观察到肝组织有显著的代谢增强。在PD大鼠模型中，给予这两种配方均对动物的行为功能产生了积极影响。
我们的研究结果表明，给予CMA1和CMA2均显著改善了代谢和行为结果，这与神经组织学观察结果一致。这些发现强调了给予CMA2作为增强AD和PD患者代谢参数和认知功能的有效治疗策略的前景。
