Cargando…

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

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 set...

Descripción completa

Detalles Bibliográficos
Autores principales: Fatoki, Toluwase Hezekiah, Chukwuejim, Stanley, Udenigwe, Chibuike C., Aluko, Rotimi E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058213/
https://www.ncbi.nlm.nih.gov/pubmed/36982902
http://dx.doi.org/10.3390/ijms24065828
_version_ 1785016570210156544
author Fatoki, Toluwase Hezekiah
Chukwuejim, Stanley
Udenigwe, Chibuike C.
Aluko, Rotimi E.
author_facet Fatoki, Toluwase Hezekiah
Chukwuejim, Stanley
Udenigwe, Chibuike C.
Aluko, Rotimi E.
author_sort Fatoki, Toluwase Hezekiah
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10058213
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100582132023-03-30 In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis Fatoki, Toluwase Hezekiah Chukwuejim, Stanley Udenigwe, Chibuike C. Aluko, Rotimi E. Int J Mol Sci Article 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. MDPI 2023-03-18 /pmc/articles/PMC10058213/ /pubmed/36982902 http://dx.doi.org/10.3390/ijms24065828 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fatoki, Toluwase Hezekiah
Chukwuejim, Stanley
Udenigwe, Chibuike C.
Aluko, Rotimi E.
In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis
title In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis
title_full In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis
title_fullStr In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis
title_full_unstemmed In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis
title_short In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis
title_sort in silico exploration of metabolically active peptides as potential therapeutic agents against amyotrophic lateral sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058213/
https://www.ncbi.nlm.nih.gov/pubmed/36982902
http://dx.doi.org/10.3390/ijms24065828
work_keys_str_mv AT fatokitoluwasehezekiah insilicoexplorationofmetabolicallyactivepeptidesaspotentialtherapeuticagentsagainstamyotrophiclateralsclerosis
AT chukwuejimstanley insilicoexplorationofmetabolicallyactivepeptidesaspotentialtherapeuticagentsagainstamyotrophiclateralsclerosis
AT udenigwechibuikec insilicoexplorationofmetabolicallyactivepeptidesaspotentialtherapeuticagentsagainstamyotrophiclateralsclerosis
AT alukorotimie insilicoexplorationofmetabolicallyactivepeptidesaspotentialtherapeuticagentsagainstamyotrophiclateralsclerosis