Mitochondrial Dysfunction in Repeat Expansion Diseases
Repeat expansion diseases are a group of neuromuscular and neurodegenerative disorders characterized by expansions of several successive repeated DNA sequences. Currently, more than 50 repeat expansion diseases have been described. These disorders involve diverse pathogenic mechanisms, including los...
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MDPI AG
2023-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/8/1593 |
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| author | Alberto Giménez-Bejarano Eva Alegre-Cortés Sokhna M. S. Yakhine-Diop Patricia Gómez-Suaga José M. Fuentes |
| author_facet | Alberto Giménez-Bejarano Eva Alegre-Cortés Sokhna M. S. Yakhine-Diop Patricia Gómez-Suaga José M. Fuentes |
| author_sort | Alberto Giménez-Bejarano |
| collection | DOAJ |
| description | Repeat expansion diseases are a group of neuromuscular and neurodegenerative disorders characterized by expansions of several successive repeated DNA sequences. Currently, more than 50 repeat expansion diseases have been described. These disorders involve diverse pathogenic mechanisms, including loss-of-function mechanisms, toxicity associated with repeat RNA, or repeat-associated non-ATG (RAN) products, resulting in impairments of cellular processes and damaged organelles. Mitochondria, double membrane organelles, play a crucial role in cell energy production, metabolic processes, calcium regulation, redox balance, and apoptosis regulation. Its dysfunction has been implicated in the pathogenesis of repeat expansion diseases. In this review, we provide an overview of the signaling pathways or proteins involved in mitochondrial functioning described in these disorders. The focus of this review will be on the analysis of published data related to three representative repeat expansion diseases: Huntington’s disease, <i>C9orf72</i>-frontotemporal dementia/amyotrophic lateral sclerosis, and myotonic dystrophy type 1. We will discuss the common effects observed in all three repeat expansion disorders and their differences. Additionally, we will address the current gaps in knowledge and propose possible new lines of research. Importantly, this group of disorders exhibit alterations in mitochondrial dynamics and biogenesis, with specific proteins involved in these processes having been identified. Understanding the underlying mechanisms of mitochondrial alterations in these disorders can potentially lead to the development of neuroprotective strategies. |
| first_indexed | 2024-03-11T00:10:45Z |
| format | Article |
| id | doaj.art-9988c958d61541f3bdb80da928bbde9b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T00:10:45Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-9988c958d61541f3bdb80da928bbde9b2023-11-19T00:02:26ZengMDPI AGAntioxidants2076-39212023-08-01128159310.3390/antiox12081593Mitochondrial Dysfunction in Repeat Expansion DiseasesAlberto Giménez-Bejarano0Eva Alegre-Cortés1Sokhna M. S. Yakhine-Diop2Patricia Gómez-Suaga3José M. Fuentes4Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, SpainDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, SpainDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, SpainDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, SpainDepartamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, SpainRepeat expansion diseases are a group of neuromuscular and neurodegenerative disorders characterized by expansions of several successive repeated DNA sequences. Currently, more than 50 repeat expansion diseases have been described. These disorders involve diverse pathogenic mechanisms, including loss-of-function mechanisms, toxicity associated with repeat RNA, or repeat-associated non-ATG (RAN) products, resulting in impairments of cellular processes and damaged organelles. Mitochondria, double membrane organelles, play a crucial role in cell energy production, metabolic processes, calcium regulation, redox balance, and apoptosis regulation. Its dysfunction has been implicated in the pathogenesis of repeat expansion diseases. In this review, we provide an overview of the signaling pathways or proteins involved in mitochondrial functioning described in these disorders. The focus of this review will be on the analysis of published data related to three representative repeat expansion diseases: Huntington’s disease, <i>C9orf72</i>-frontotemporal dementia/amyotrophic lateral sclerosis, and myotonic dystrophy type 1. We will discuss the common effects observed in all three repeat expansion disorders and their differences. Additionally, we will address the current gaps in knowledge and propose possible new lines of research. Importantly, this group of disorders exhibit alterations in mitochondrial dynamics and biogenesis, with specific proteins involved in these processes having been identified. Understanding the underlying mechanisms of mitochondrial alterations in these disorders can potentially lead to the development of neuroprotective strategies.https://www.mdpi.com/2076-3921/12/8/1593Huntington disease<i>C9orf72</i>myotonic dystrophy type 1Ca<sup>2+</sup>, mitophagyapoptosisROS |
| spellingShingle | Alberto Giménez-Bejarano Eva Alegre-Cortés Sokhna M. S. Yakhine-Diop Patricia Gómez-Suaga José M. Fuentes Mitochondrial Dysfunction in Repeat Expansion Diseases Antioxidants Huntington disease <i>C9orf72</i> myotonic dystrophy type 1 Ca<sup>2+</sup>, mitophagy apoptosis ROS |
| title | Mitochondrial Dysfunction in Repeat Expansion Diseases |
| title_full | Mitochondrial Dysfunction in Repeat Expansion Diseases |
| title_fullStr | Mitochondrial Dysfunction in Repeat Expansion Diseases |
| title_full_unstemmed | Mitochondrial Dysfunction in Repeat Expansion Diseases |
| title_short | Mitochondrial Dysfunction in Repeat Expansion Diseases |
| title_sort | mitochondrial dysfunction in repeat expansion diseases |
| topic | Huntington disease <i>C9orf72</i> myotonic dystrophy type 1 Ca<sup>2+</sup>, mitophagy apoptosis ROS |
| url | https://www.mdpi.com/2076-3921/12/8/1593 |
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