Molecular and Cellular Mechanisms Affected in ALS
Amyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cel...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/10/3/101 |
| _version_ | 1797555717346951168 |
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| author | Laura Le Gall Ekene Anakor Owen Connolly Udaya Geetha Vijayakumar William J. Duddy Stephanie Duguez |
| author_facet | Laura Le Gall Ekene Anakor Owen Connolly Udaya Geetha Vijayakumar William J. Duddy Stephanie Duguez |
| author_sort | Laura Le Gall |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cellular processes in ALS pathology, a cohesive understanding of which may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches. Here, the different pathways that have been investigated in ALS are summarized, discussing in detail: mitochondrial dysfunction, oxidative stress, axonal transport dysregulation, glutamate excitotoxicity, endosomal and vesicular transport impairment, impaired protein homeostasis, and aberrant RNA metabolism. This review considers the mechanistic roles of ALS-associated genes in pathology, viewed through the prism of shared molecular pathways. |
| first_indexed | 2024-03-10T16:51:26Z |
| format | Article |
| id | doaj.art-11600447c0c24c74bb6c7d1776befaba |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T16:51:26Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-11600447c0c24c74bb6c7d1776befaba2023-11-20T11:16:05ZengMDPI AGJournal of Personalized Medicine2075-44262020-08-0110310110.3390/jpm10030101Molecular and Cellular Mechanisms Affected in ALSLaura Le Gall0Ekene Anakor1Owen Connolly2Udaya Geetha Vijayakumar3William J. Duddy4Stephanie Duguez5Northern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry-Londonderry BT47, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry-Londonderry BT47, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry-Londonderry BT47, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry-Londonderry BT47, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry-Londonderry BT47, UKNorthern Ireland Center for Stratified/Personalised Medicine, Biomedical Sciences Research Institute, Ulster University, Derry-Londonderry BT47, UKAmyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cellular processes in ALS pathology, a cohesive understanding of which may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches. Here, the different pathways that have been investigated in ALS are summarized, discussing in detail: mitochondrial dysfunction, oxidative stress, axonal transport dysregulation, glutamate excitotoxicity, endosomal and vesicular transport impairment, impaired protein homeostasis, and aberrant RNA metabolism. This review considers the mechanistic roles of ALS-associated genes in pathology, viewed through the prism of shared molecular pathways.https://www.mdpi.com/2075-4426/10/3/101oxidative stressmitochondria dysfunctionaxonal transportautophagyendocytosissecretion |
| spellingShingle | Laura Le Gall Ekene Anakor Owen Connolly Udaya Geetha Vijayakumar William J. Duddy Stephanie Duguez Molecular and Cellular Mechanisms Affected in ALS Journal of Personalized Medicine oxidative stress mitochondria dysfunction axonal transport autophagy endocytosis secretion |
| title | Molecular and Cellular Mechanisms Affected in ALS |
| title_full | Molecular and Cellular Mechanisms Affected in ALS |
| title_fullStr | Molecular and Cellular Mechanisms Affected in ALS |
| title_full_unstemmed | Molecular and Cellular Mechanisms Affected in ALS |
| title_short | Molecular and Cellular Mechanisms Affected in ALS |
| title_sort | molecular and cellular mechanisms affected in als |
| topic | oxidative stress mitochondria dysfunction axonal transport autophagy endocytosis secretion |
| url | https://www.mdpi.com/2075-4426/10/3/101 |
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