Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies
The inherited peripheral neuropathies (IPNs) comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00143/full |
| _version_ | 1828873184465649664 |
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| author | Mansour Haidar Vincent Timmerman |
| author_facet | Mansour Haidar Vincent Timmerman |
| author_sort | Mansour Haidar |
| collection | DOAJ |
| description | The inherited peripheral neuropathies (IPNs) comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pathomechanism among the different phenotypes has become the holy grail of functional research into IPNs. During the last decade, studies on several affected genes have shown a direct and/or indirect correlation with autophagy. Autophagy, a cellular homeostatic process, is required for the removal of cell aggregates, long-lived proteins and dead organelles from the cell in double-membraned vesicles destined for the lysosomes. As an evolutionarily highly conserved process, autophagy is essential for the survival and proper functioning of the cell. Recently, neuronal cells have been shown to be particularly vulnerable to disruption of the autophagic pathway. Furthermore, autophagy has been shown to be affected in various common neurodegenerative diseases of both the central and the peripheral nervous system including Alzheimer’s, Parkinson’s, and Huntington’s diseases. In this review we provide an overview of the genes involved in hereditary neuropathies which are linked to autophagy and we propose the disruption of the autophagic flux as an emerging common pathomechanism. We also shed light on the different steps of the autophagy pathway linked to these genes. Finally, we review the concept of autophagy being a therapeutic target in IPNs, and the possibilities and challenges of this pathway-specific targeting. |
| first_indexed | 2024-12-13T07:11:02Z |
| format | Article |
| id | doaj.art-06592b5e8eb340e5a36e3479038bfe17 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-13T07:11:02Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-06592b5e8eb340e5a36e3479038bfe172022-12-21T23:55:40ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-05-011010.3389/fnmol.2017.00143270143Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral NeuropathiesMansour HaidarVincent TimmermanThe inherited peripheral neuropathies (IPNs) comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pathomechanism among the different phenotypes has become the holy grail of functional research into IPNs. During the last decade, studies on several affected genes have shown a direct and/or indirect correlation with autophagy. Autophagy, a cellular homeostatic process, is required for the removal of cell aggregates, long-lived proteins and dead organelles from the cell in double-membraned vesicles destined for the lysosomes. As an evolutionarily highly conserved process, autophagy is essential for the survival and proper functioning of the cell. Recently, neuronal cells have been shown to be particularly vulnerable to disruption of the autophagic pathway. Furthermore, autophagy has been shown to be affected in various common neurodegenerative diseases of both the central and the peripheral nervous system including Alzheimer’s, Parkinson’s, and Huntington’s diseases. In this review we provide an overview of the genes involved in hereditary neuropathies which are linked to autophagy and we propose the disruption of the autophagic flux as an emerging common pathomechanism. We also shed light on the different steps of the autophagy pathway linked to these genes. Finally, we review the concept of autophagy being a therapeutic target in IPNs, and the possibilities and challenges of this pathway-specific targeting.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00143/fullautophagyhereditary neuropathiesCharcot-Marie-Toothneurodegenerationproteostasis |
| spellingShingle | Mansour Haidar Vincent Timmerman Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies Frontiers in Molecular Neuroscience autophagy hereditary neuropathies Charcot-Marie-Tooth neurodegeneration proteostasis |
| title | Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies |
| title_full | Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies |
| title_fullStr | Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies |
| title_full_unstemmed | Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies |
| title_short | Autophagy as an Emerging Common Pathomechanism in Inherited Peripheral Neuropathies |
| title_sort | autophagy as an emerging common pathomechanism in inherited peripheral neuropathies |
| topic | autophagy hereditary neuropathies Charcot-Marie-Tooth neurodegeneration proteostasis |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00143/full |
| work_keys_str_mv | AT mansourhaidar autophagyasanemergingcommonpathomechanismininheritedperipheralneuropathies AT vincenttimmerman autophagyasanemergingcommonpathomechanismininheritedperipheralneuropathies |