In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis

被引:4
|
作者
Fatoki, Toluwase Hezekiah [1 ]
Chukwuejim, Stanley [1 ,2 ]
Udenigwe, Chibuike C. [3 ,4 ]
Aluko, Rotimi E. [2 ,5 ]
机构
[1] Fed Univ Oye Ekiti, Dept Biochem, PMB 373, Oye 371104, Nigeria
[2] Univ Manitoba, Dept Food & Human Nutr Sci, Winnipeg, MB R3T 2N2, Canada
[3] Univ Ottawa, Fac Hlth Sci, Sch Nutr Sci, Ottawa, ON K1H 8M5, Canada
[4] Univ Ottawa, Fac Sci, Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada
[5] Univ Manitoba, Richardson Ctr Food Technol & Res, Winnipeg, MB R3T 2N2, Canada
关键词
amyotrophic lateral sclerosis; ALS; associated genes; hydrolysate peptides; pharmacokinetics; target prediction; metabolic; supplements; molecular docking; TRANSGENIC MOUSE MODEL; PROTECTS MOTOR-NEURONS; BLOOD-BRAIN-BARRIER; SPINAL-CORD; APOPTOSIS PROTEIN; CYCLOOXYGENASE-2; INHIBITION; GENE; XIAP; CLEAVAGE;
D O I
10.3390/ijms24065828
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:22
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