A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis
IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the deterioration of upper and lower motor neurons. Affected patients experience progressive muscle weakness, including difficulty in swallowing and breathing; being respiratory failure...
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2025-06-01
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| author | Carlos A. Arreola-Aldape Carlos A. Arreola-Aldape Carlos A. Arreola-Aldape Jose A. Moran-Guerrero Jose A. Moran-Guerrero Guillermo K. Pons-Monnier Guillermo K. Pons-Monnier Rogelio E. Flores-Salcido Rogelio E. Flores-Salcido Emmanuel Martinez-Ledesma Emmanuel Martinez-Ledesma Luis M. Ruiz-Manriquez Luis M. Ruiz-Manriquez K. Rebeca Razo-Alvarez K. Rebeca Razo-Alvarez Daniela Mares-Custodio Daniela Mares-Custodio Pablo J. Avalos-Montes Pablo J. Avalos-Montes Jose A. Figueroa-Sanchez Jose A. Figueroa-Sanchez Rocio Ortiz-Lopez Rocio Ortiz-Lopez Rocio Ortiz-Lopez Hector R. Martínez Hector R. Martínez Raquel Cuevas-Diaz Duran Raquel Cuevas-Diaz Duran |
| author_facet | Carlos A. Arreola-Aldape Carlos A. Arreola-Aldape Carlos A. Arreola-Aldape Jose A. Moran-Guerrero Jose A. Moran-Guerrero Guillermo K. Pons-Monnier Guillermo K. Pons-Monnier Rogelio E. Flores-Salcido Rogelio E. Flores-Salcido Emmanuel Martinez-Ledesma Emmanuel Martinez-Ledesma Luis M. Ruiz-Manriquez Luis M. Ruiz-Manriquez K. Rebeca Razo-Alvarez K. Rebeca Razo-Alvarez Daniela Mares-Custodio Daniela Mares-Custodio Pablo J. Avalos-Montes Pablo J. Avalos-Montes Jose A. Figueroa-Sanchez Jose A. Figueroa-Sanchez Rocio Ortiz-Lopez Rocio Ortiz-Lopez Rocio Ortiz-Lopez Hector R. Martínez Hector R. Martínez Raquel Cuevas-Diaz Duran Raquel Cuevas-Diaz Duran |
| author_sort | Carlos A. Arreola-Aldape |
| collection | DOAJ |
| description | IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the deterioration of upper and lower motor neurons. Affected patients experience progressive muscle weakness, including difficulty in swallowing and breathing; being respiratory failure the main cause of death. However, there is considerable phenotypic heterogeneity, and its diagnosis is based on clinical criteria. Moreover, most ALS cases remain unexplained, suggesting a complex genetic background.MethodsTo better understand the molecular mechanisms underlying ALS, we comprehensively analyzed, filtered and classified genes from 4,293 abstracts retrieved from PubMed, 7,343 variants from ClinVar, and 33 study accessions from GWAS catalog. To address the importance of ALS-associated genes and variants, we performed diverse bioinformatic analyses, including gene set enrichment, drug-gene interactions, and differential gene expression analysis using public databases.ResultsOur analysis yielded a catalog of 300 genes with 479 ALS-associated variants. Most of these genes and variants are found in coding regions and their proteins are allocated to the cytoplasm and the nucleus, underscoring the relevance of toxic protein aggregates. Moreover, protein-coding genes enriched ALS-specific pathways, for example spasticity, dysarthria and dyspnea. ALS-associated genes are targeted by commonly used drugs, including Riluzole and Edaravone, and by the recently approved antisense oligonucleotide therapy (Tofersen). Moreover, we observed transcriptional dysregulation of ALS-associated genes in peripheral blood mononuclear cell and postmortem cortex samples.ConclusionOverall, this ALS catalog can serve as a foundational tool for advancing early diagnosis, identifying biomarkers, and developing personalized therapeutic strategies. |
| format | Article |
| id | doaj-art-a4b7f0feea9d49bfa0ca7a46ca939ca7 |
| institution | DOAJ |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-a4b7f0feea9d49bfa0ca7a46ca939ca72025-08-20T03:20:14ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-06-011910.3389/fnins.2025.15983361598336A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosisCarlos A. Arreola-Aldape0Carlos A. Arreola-Aldape1Carlos A. Arreola-Aldape2Jose A. Moran-Guerrero3Jose A. Moran-Guerrero4Guillermo K. Pons-Monnier5Guillermo K. Pons-Monnier6Rogelio E. Flores-Salcido7Rogelio E. Flores-Salcido8Emmanuel Martinez-Ledesma9Emmanuel Martinez-Ledesma10Luis M. Ruiz-Manriquez11Luis M. Ruiz-Manriquez12K. Rebeca Razo-Alvarez13K. Rebeca Razo-Alvarez14Daniela Mares-Custodio15Daniela Mares-Custodio16Pablo J. Avalos-Montes17Pablo J. Avalos-Montes18Jose A. Figueroa-Sanchez19Jose A. Figueroa-Sanchez20Rocio Ortiz-Lopez21Rocio Ortiz-Lopez22Rocio Ortiz-Lopez23Hector R. Martínez24Hector R. Martínez25Raquel Cuevas-Diaz Duran26Raquel Cuevas-Diaz Duran27Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoDepartment of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoTecnologico de Monterrey, Institute for Obesity Research, Monterrey, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoTecnologico de Monterrey, Institute for Obesity Research, Monterrey, MexicoTecnologico de Monterrey, Proyecto oriGen, Monterrey, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, MexicoInstituto de Neurología y Neurocirugía, Centro Médico Zambrano Hellion, TecSalud, San Pedro Garza Garcia, MexicoIntroductionAmyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the deterioration of upper and lower motor neurons. Affected patients experience progressive muscle weakness, including difficulty in swallowing and breathing; being respiratory failure the main cause of death. However, there is considerable phenotypic heterogeneity, and its diagnosis is based on clinical criteria. Moreover, most ALS cases remain unexplained, suggesting a complex genetic background.MethodsTo better understand the molecular mechanisms underlying ALS, we comprehensively analyzed, filtered and classified genes from 4,293 abstracts retrieved from PubMed, 7,343 variants from ClinVar, and 33 study accessions from GWAS catalog. To address the importance of ALS-associated genes and variants, we performed diverse bioinformatic analyses, including gene set enrichment, drug-gene interactions, and differential gene expression analysis using public databases.ResultsOur analysis yielded a catalog of 300 genes with 479 ALS-associated variants. Most of these genes and variants are found in coding regions and their proteins are allocated to the cytoplasm and the nucleus, underscoring the relevance of toxic protein aggregates. Moreover, protein-coding genes enriched ALS-specific pathways, for example spasticity, dysarthria and dyspnea. ALS-associated genes are targeted by commonly used drugs, including Riluzole and Edaravone, and by the recently approved antisense oligonucleotide therapy (Tofersen). Moreover, we observed transcriptional dysregulation of ALS-associated genes in peripheral blood mononuclear cell and postmortem cortex samples.ConclusionOverall, this ALS catalog can serve as a foundational tool for advancing early diagnosis, identifying biomarkers, and developing personalized therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fnins.2025.1598336/fullAmyotrophic Lateral Sclerosissystematic reviewgenesvariantsmutations |
| spellingShingle | Carlos A. Arreola-Aldape Carlos A. Arreola-Aldape Carlos A. Arreola-Aldape Jose A. Moran-Guerrero Jose A. Moran-Guerrero Guillermo K. Pons-Monnier Guillermo K. Pons-Monnier Rogelio E. Flores-Salcido Rogelio E. Flores-Salcido Emmanuel Martinez-Ledesma Emmanuel Martinez-Ledesma Luis M. Ruiz-Manriquez Luis M. Ruiz-Manriquez K. Rebeca Razo-Alvarez K. Rebeca Razo-Alvarez Daniela Mares-Custodio Daniela Mares-Custodio Pablo J. Avalos-Montes Pablo J. Avalos-Montes Jose A. Figueroa-Sanchez Jose A. Figueroa-Sanchez Rocio Ortiz-Lopez Rocio Ortiz-Lopez Rocio Ortiz-Lopez Hector R. Martínez Hector R. Martínez Raquel Cuevas-Diaz Duran Raquel Cuevas-Diaz Duran A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis Frontiers in Neuroscience Amyotrophic Lateral Sclerosis systematic review genes variants mutations |
| title | A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis |
| title_full | A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis |
| title_fullStr | A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis |
| title_full_unstemmed | A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis |
| title_short | A systematic review and functional in-silico analysis of genes and variants associated with amyotrophic lateral sclerosis |
| title_sort | systematic review and functional in silico analysis of genes and variants associated with amyotrophic lateral sclerosis |
| topic | Amyotrophic Lateral Sclerosis systematic review genes variants mutations |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1598336/full |
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