Department of Biochemistry, Federal University Oye-Ekiti, PMB 373, Oye 371104, Nigeria.
Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Int J Mol Sci. 2023 Mar 18;24(6):5828. doi: 10.3390/ijms24065828.
Amyotrophic lateral sclerosis (ALS) is regarded as a fatal neurodegenerative disease that is featured by progressive damage of the upper and lower motor neurons. To date, over 45 genes have been found to be connected with ALS pathology. The aim of this work was to computationally identify unique sets of protein hydrolysate peptides that could serve as therapeutic agents against ALS. Computational methods which include target prediction, protein-protein interaction, and peptide-protein molecular docking were used. The results showed that the network of critical ALS-associated genes consists of ATG16L2, SCFD1, VAC15, VEGFA, KEAP1, KIF5A, FIG4, TUBA4A, SIGMAR1, SETX, ANXA11, HNRNPL, NEK1, C9orf72, VCP, RPSA, ATP5B, and SOD1 together with predicted kinases such as AKT1, CDK4, DNAPK, MAPK14, and ERK2 in addition to transcription factors such as MYC, RELA, ZMIZ1, EGR1, TRIM28, and FOXA2. The identified molecular targets of the peptides that support multi-metabolic components in ALS pathogenesis include cyclooxygenase-2, angiotensin I-converting enzyme, dipeptidyl peptidase IV, X-linked inhibitor of apoptosis protein 3, and endothelin receptor ET-A. Overall, the results showed that AGL, APL, AVK, IIW, PVI, and VAY peptides are promising candidates for further study. Future work would be needed to validate the therapeutic properties of these hydrolysate peptides by in vitro and in vivo approaches.
肌萎缩侧索硬化症（ALS）被认为是一种致命的神经退行性疾病，其特征是上下运动神经元的进行性损伤。迄今为止，已经发现超过 45 个基因与 ALS 病理有关。本工作的目的是通过计算鉴定出独特的蛋白质水解肽集，作为治疗 ALS 的药物。使用了包括靶标预测、蛋白质-蛋白质相互作用和肽-蛋白质分子对接在内的计算方法。结果表明，关键 ALS 相关基因网络由 ATG16L2、SCFD1、VAC15、VEGFA、KEAP1、KIF5A、FIG4、TUBA4A、SIGMAR1、SETX、ANXA11、HNRNPL、NEK1、C9orf72、VCP、RPSA、ATP5B 和 SOD1 以及预测激酶 AKT1、CDK4、DNAPK、MAPK14 和 ERK2 组成，此外还有转录因子 MYC、RELA、ZMIZ1、EGR1、TRIM28 和 FOXA2。支持 ALS 发病机制中多代谢成分的肽的鉴定分子靶标包括环氧化酶-2、血管紧张素 I 转换酶、二肽基肽酶 IV、X 连锁凋亡蛋白抑制剂 3 和内皮素受体 ET-A。总的来说，结果表明 AGL、APL、AVK、IIW、PVI 和 VAY 肽是进一步研究的有前途的候选物。需要进一步的工作来通过体外和体内方法验证这些水解肽的治疗特性。
