Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)
The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to e...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/9/10/1020 |
| _version_ | 1797550408747450368 |
|---|---|
| author | Isabel Hinarejos Candela Machuca Paula Sancho Carmen Espinós |
| author_facet | Isabel Hinarejos Candela Machuca Paula Sancho Carmen Espinós |
| author_sort | Isabel Hinarejos |
| collection | DOAJ |
| description | The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes <i>PANK2</i>, <i>PLA2G6</i>, <i>WDR45</i>, <i>C19ORF12</i>, <i>FA2H</i>, <i>ATP13A2</i>, <i>COASY</i>, <i>FTL1</i>, <i>CP</i>, and <i>DCAF17</i>. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation. |
| first_indexed | 2024-03-10T15:28:52Z |
| format | Article |
| id | doaj.art-ac9fe3fff7084b0c9614b8aebba6b30b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T15:28:52Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-ac9fe3fff7084b0c9614b8aebba6b30b2023-11-20T17:48:41ZengMDPI AGAntioxidants2076-39212020-10-01910102010.3390/antiox9101020Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)Isabel Hinarejos0Candela Machuca1Paula Sancho2Carmen Espinós3Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, SpainUnit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, SpainUnit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, SpainUnit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, SpainThe syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes <i>PANK2</i>, <i>PLA2G6</i>, <i>WDR45</i>, <i>C19ORF12</i>, <i>FA2H</i>, <i>ATP13A2</i>, <i>COASY</i>, <i>FTL1</i>, <i>CP</i>, and <i>DCAF17</i>. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation.https://www.mdpi.com/2076-3921/9/10/1020neurodegenerative disorderbrain iron accumulationrare diseasemitochondrial dysfunctionoxidative stressneuroinflammation |
| spellingShingle | Isabel Hinarejos Candela Machuca Paula Sancho Carmen Espinós Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA) Antioxidants neurodegenerative disorder brain iron accumulation rare disease mitochondrial dysfunction oxidative stress neuroinflammation |
| title | Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA) |
| title_full | Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA) |
| title_fullStr | Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA) |
| title_full_unstemmed | Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA) |
| title_short | Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA) |
| title_sort | mitochondrial dysfunction oxidative stress and neuroinflammation in neurodegeneration with brain iron accumulation nbia |
| topic | neurodegenerative disorder brain iron accumulation rare disease mitochondrial dysfunction oxidative stress neuroinflammation |
| url | https://www.mdpi.com/2076-3921/9/10/1020 |
| work_keys_str_mv | AT isabelhinarejos mitochondrialdysfunctionoxidativestressandneuroinflammationinneurodegenerationwithbrainironaccumulationnbia AT candelamachuca mitochondrialdysfunctionoxidativestressandneuroinflammationinneurodegenerationwithbrainironaccumulationnbia AT paulasancho mitochondrialdysfunctionoxidativestressandneuroinflammationinneurodegenerationwithbrainironaccumulationnbia AT carmenespinos mitochondrialdysfunctionoxidativestressandneuroinflammationinneurodegenerationwithbrainironaccumulationnbia |