Ubaid Saba, Pandey Shivani, Akhtar Mohd Sohail, Rumman Mohammad, Singh Babita, Mahdi Abbas Ali
Department of Biochemistry, King George's Medical University (KGMU), Lucknow 226003, Uttar Pradesh, India.
Division of Molecular & Structural Biology, Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India.
ACS Chem Neurosci. 2022 Apr 20;13(8):1263-1272. doi: 10.1021/acschemneuro.1c00876. Epub 2022 Apr 6.
Parkinson's disease (PD) is the second most common devastating neurodegenerative disorder. Presently used therapies for PD have severe side effects and are limited to only temporary improvement. Therefore, a new therapeutic approach to treat PD urgently needs to be developed. α-Lactalbumin, the most abundant milk protein in camel milk, has been attributed to various medicinal properties. This study intended to investigate the neuroprotective efficacy of the camel α-lactalbumin and oleic acid (CLOA) complex. One mechanism postulated to underlie neuroprotection by the CLOA complex is the induction of silent information regulatory protein (SIRT1). SIRT1 is known to be involved in several pathological and physiological processes, and it has been suggested that SIRT1 plays a protective role in PD. Oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis are involved in PD pathogenesis. Our results revealed that SIRT1 inhibits oxidative stress by maintaining HIF-1α in a deacetylated state. SIRT1 upregulates the expression of FOXO3a and HSF-1, thus inhibiting apoptosis and maintaining the homeostasis of cellular proteins. Increased SIRT1 expression reduces the levels of TNF-α, IL-6, and IL-8, which in turn inhibits neuroinflammation. In addition to SIRT1, the CLOA complex also enhances the expression of survivin and leptin and promotes the survival of neuroblastoma cells. Altogether, our results suggest that the CLOA complex might be a novel therapeutic molecule that could ameliorate neuronal cell damage in PD.
帕金森病（PD）是第二常见的毁灭性神经退行性疾病。目前用于治疗PD的疗法有严重的副作用，且仅限于暂时改善症状。因此，迫切需要开发一种新的治疗PD的方法。α-乳白蛋白是骆驼奶中最丰富的乳蛋白，具有多种药用特性。本研究旨在探讨骆驼α-乳白蛋白与油酸（CLOA）复合物的神经保护作用。CLOA复合物发挥神经保护作用的一种假定机制是诱导沉默信息调节蛋白（SIRT1）。已知SIRT1参与多种病理和生理过程，并且有人提出SIRT1在PD中起保护作用。氧化应激、炎症、线粒体功能障碍和细胞凋亡都参与了PD的发病机制。我们的结果显示，SIRT1通过维持缺氧诱导因子-1α（HIF-1α）处于去乙酰化状态来抑制氧化应激。SIRT1上调叉头框蛋白O3a（FOXO3a）和热休克因子-1（HSF-1）的表达，从而抑制细胞凋亡并维持细胞蛋白质的稳态。SIRT1表达增加会降低肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）的水平，进而抑制神经炎症。除了SIRT1，CLOA复合物还能增强生存素和瘦素的表达，并促进神经母细胞瘤细胞的存活。总之，我们的结果表明，CLOA复合物可能是一种新型治疗分子，可改善PD中的神经元细胞损伤。
