Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein agg...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9832 |
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| author | Milena Jankovic Ivana Novakovic Phepy Gamil Anwar Dawod Ayman Gamil Anwar Dawod Aleksandra Drinic Fayda I. Abdel Motaleb Sinisa Ducic Dejan Nikolic |
| author_facet | Milena Jankovic Ivana Novakovic Phepy Gamil Anwar Dawod Ayman Gamil Anwar Dawod Aleksandra Drinic Fayda I. Abdel Motaleb Sinisa Ducic Dejan Nikolic |
| author_sort | Milena Jankovic |
| collection | DOAJ |
| description | Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly. |
| first_indexed | 2024-03-10T07:35:37Z |
| format | Article |
| id | doaj.art-43ef9e8f3a1a4845bca3b862622cca44 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:37Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-43ef9e8f3a1a4845bca3b862622cca442023-11-22T13:28:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218983210.3390/ijms22189832Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral SclerosisMilena Jankovic0Ivana Novakovic1Phepy Gamil Anwar Dawod2Ayman Gamil Anwar Dawod3Aleksandra Drinic4Fayda I. Abdel Motaleb5Sinisa Ducic6Dejan Nikolic7Neurology Clinic, Clinical Center of Serbia, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaInternal Medicine, Hepatogastroenterology and Endoscopy Department, Faculty of Medicine, Ain Shams University, 11591 Cairo, EgyptFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, 11591 Cairo, EgyptFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaAmyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly.https://www.mdpi.com/1422-0067/22/18/9832amyotrophic lateral sclerosisgenesmitochondriabiomarkerstherapy |
| spellingShingle | Milena Jankovic Ivana Novakovic Phepy Gamil Anwar Dawod Ayman Gamil Anwar Dawod Aleksandra Drinic Fayda I. Abdel Motaleb Sinisa Ducic Dejan Nikolic Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis International Journal of Molecular Sciences amyotrophic lateral sclerosis genes mitochondria biomarkers therapy |
| title | Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis |
| title_full | Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis |
| title_fullStr | Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis |
| title_short | Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis |
| title_sort | current concepts on genetic aspects of mitochondrial dysfunction in amyotrophic lateral sclerosis |
| topic | amyotrophic lateral sclerosis genes mitochondria biomarkers therapy |
| url | https://www.mdpi.com/1422-0067/22/18/9832 |
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