Panorama de los mecanismos moleculares y celulares que subyacen la esclerosis lateral amiotrófica
Overview of the molecular and cellular mechanisms underlying amyotrophic lateral sclerosis

Diego Bratta Castro, Melissa Bravo

Resumen


RESUMEN
La Esclerosis Lateral Amiotrófica (ELA) es una patología neurodegenerativa caracterizada por la pérdida progresiva de motoneuronas, su pronóstico de vida se limita a los 3-5 años tras el inicio de los síntomas. En la fisiopatología de la enfermedad se identifican varios mecanismos moleculares y celulares alterados que contribuyen a su progresión como la enzima superóxido dismutasa 1 (SOD1), la proteína de unión al ADN TAR (TARDBP) y la proteína de unión al ARN fusionada en sarcoma (FUS) y el gen C9ORF72, sin embargo, los mecanismos subyacentes aún no se comprenden totalmente. Como objetivo nos planteamos proporcionar una revisión actualizada de los mecanismos moleculares y celulares que subyacen la esclerosis lateral amiotrófica (ELA). Se realizó mediante una búsqueda bibliográfica en las siguientes bases de datos: Medline, Web of Science y Scopus, priorizando estudios recientes y de alto impacto de los últimos 5 años. Se analizaron los posibles biomarcadores diagnósticos y los mecanismos moleculares asociados. Los resultados destacan la utilidad potencial de marcadores como neurofilamentos (NfL, pNfH), quitinasas y microRNAs (miR-206, miR-133a). Además, se destaca la importancia de los biomarcadores de inflamación, de estrés oxidativo, bioquímicos como pruebas diagnósticas complementarias. Se identificaron nuevas variantes genéticas en poblaciones asiáticas y se exploró la relación entre el eje intestino-cerebro y la progresión de la enfermedad. En conclusión, los mecanismos moleculares y vías de señalización siguen sin esclarecerse. La identificación de marcadores es clave para el diagnóstico temprano y mejorar el pronóstico de los pacientes.

ABSTRACT
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons, and its life expectancy is limited to 3-5 years after the onset of symptoms. Several altered molecular and cellular mechanisms have been identified in the pathophysiology of the disease that contribute to its progression, such as the enzyme superoxide dismutase 1 (SOD1), the TAR DNA-binding protein (TARDBP), the fused sarcoma RNA-binding protein (FUS), and the C9ORF72 gene. However, the underlying mechanisms are still not fully understood. Our objective was to provide an updated review of the molecular and cellular mechanisms underlying amyotrophic lateral sclerosis (ALS). This was done through a bibliographic search in the following databases: Medline, Web of Science, and Scopus, prioritizing recent and high-impact studies from the last 5 years. Possible diagnostic biomarkers and associated molecular mechanisms were analyzed. The results highlight the potential usefulness of markers such as neurofilaments (NfL, pNfH), chitinases and microRNAs (miR-206, miR-133a). In addition, the importance of inflammatory, oxidative stress and biochemical biomarkers as complementary diagnostic tests is highlighted. New genetic variants were identified in Asian populations and the relationship between the gut-brain axis and disease progression was explored. In conclusion, molecular mechanisms and signaling pathways remain unclear. The identification of markers is key for early diagnosis and improving patient prognosis.

Recibido: 10-01-2025
Aprobado: 19-02-2025
Publicado: 28-02-2025


Palabras clave


esclerosis lateral amiotrófica; biomarcadores; mecanismos moleculares; amyotrophic lateral sclerosis; biomarkers; molecular mechanisms

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Referencias


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