Mitochondrial dysfunction in Down Syndrome: from pathology to therapy
Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The...
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| Format: | Article |
| Language: | English |
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Elsevier
2023
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| Online Access: | http://psasir.upm.edu.my/id/eprint/109511/ http://psasir.upm.edu.my/id/eprint/109511/1/1-s2.0-S0306452222006030-main.pdf |
| _version_ | 1848865390675886080 |
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| author | Tan, Kai-Leng Lee, Han-Chung Cheah, Pike-See Ling, King-Hwa |
| author_facet | Tan, Kai-Leng Lee, Han-Chung Cheah, Pike-See Ling, King-Hwa |
| author_sort | Tan, Kai-Leng |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The function of mitochondria is primarily regulated by genes encoded in the mitochondrion and nucleus. Many genes on HSA21 are involved in oxidative phosphorylation (OXPHOS) and regulation of mitochondrial functions. This review highlights the HSA21 dosage-sensitive nuclear-encoded mitochondrial genes associated with overexpression-related phenotypes seen in DS. This includes impaired mitochondrial dynamics, structural defects and dysregulated bioenergetic profiles such as OXPHOS deficiency and reduced ATP production. Various therapeutic approaches for modulating energy deficits in DS, effects and molecular mechanism of gene therapy and drugs that exert protective effects through modulation of mitochondrial function and attenuation of oxidative stress in DS cells were discussed. It is prudent that improving DS pathophysiological conditions or quality of life may be feasible by targeting something as simple as cellular mitochondrial biogenesis and function. |
| first_indexed | 2025-11-15T14:03:57Z |
| format | Article |
| id | upm-109511 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:03:57Z |
| publishDate | 2023 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1095112024-12-10T03:50:55Z http://psasir.upm.edu.my/id/eprint/109511/ Mitochondrial dysfunction in Down Syndrome: from pathology to therapy Tan, Kai-Leng Lee, Han-Chung Cheah, Pike-See Ling, King-Hwa Mitochondrial dysfunctions have been described in Down syndrome (DS) caused by either partial or full trisomy of chromosome 21 (HSA21). Mitochondria play a crucial role in various vital functions in eukaryotic cells, especially in energy production, calcium homeostasis and programmed cell death. The function of mitochondria is primarily regulated by genes encoded in the mitochondrion and nucleus. Many genes on HSA21 are involved in oxidative phosphorylation (OXPHOS) and regulation of mitochondrial functions. This review highlights the HSA21 dosage-sensitive nuclear-encoded mitochondrial genes associated with overexpression-related phenotypes seen in DS. This includes impaired mitochondrial dynamics, structural defects and dysregulated bioenergetic profiles such as OXPHOS deficiency and reduced ATP production. Various therapeutic approaches for modulating energy deficits in DS, effects and molecular mechanism of gene therapy and drugs that exert protective effects through modulation of mitochondrial function and attenuation of oxidative stress in DS cells were discussed. It is prudent that improving DS pathophysiological conditions or quality of life may be feasible by targeting something as simple as cellular mitochondrial biogenesis and function. Elsevier 2023-02-10 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/109511/1/1-s2.0-S0306452222006030-main.pdf Tan, Kai-Leng and Lee, Han-Chung and Cheah, Pike-See and Ling, King-Hwa (2023) Mitochondrial dysfunction in Down Syndrome: from pathology to therapy. Neuroscience, 511. pp. 1-12. ISSN 0306-4522; eISSN: 1873-7544 https://linkinghub.elsevier.com/retrieve/pii/S0306452222006030 10.1016/j.neuroscience.2022.12.003 |
| spellingShingle | Tan, Kai-Leng Lee, Han-Chung Cheah, Pike-See Ling, King-Hwa Mitochondrial dysfunction in Down Syndrome: from pathology to therapy |
| title | Mitochondrial dysfunction in Down Syndrome: from pathology to therapy |
| title_full | Mitochondrial dysfunction in Down Syndrome: from pathology to therapy |
| title_fullStr | Mitochondrial dysfunction in Down Syndrome: from pathology to therapy |
| title_full_unstemmed | Mitochondrial dysfunction in Down Syndrome: from pathology to therapy |
| title_short | Mitochondrial dysfunction in Down Syndrome: from pathology to therapy |
| title_sort | mitochondrial dysfunction in down syndrome: from pathology to therapy |
| url | http://psasir.upm.edu.my/id/eprint/109511/ http://psasir.upm.edu.my/id/eprint/109511/ http://psasir.upm.edu.my/id/eprint/109511/ http://psasir.upm.edu.my/id/eprint/109511/1/1-s2.0-S0306452222006030-main.pdf |