Progressive neurodegenerative conditions collectively cause over 9 million deaths and 276 million relevant disabilities in a single year. Not unexpectedly the decline of mitochondrial function, responsible for >90% of ATP by oxidative phosphorylation, has been well correlated with cellular pathophysiology, the deterioration of cognitive and motor function, and aging. Mitochondrial dysfunction typically includes reactive oxygen species generation, loss of mtDNA integrity, impaired mitophagy and dynamics. Cellular pathways affected by mitochondrial dysfunction evident by disease and chemical stress models include altered protein synthesis, trafficking and degradation, inflammation, and oxidative damage to nucleic acids, lipids, and proteins, which can lead to cellular dysfunction, telomere attrition, senescence, and death. While unlikely to directly reverse disease progression, therapeutics targeting mitochondrial function have demonstrated potential to mitigate neurodegeneration and age-associated cellular deterioration at the cellular and whole organism level. Encouraging examples include the reduction of ROS, peroxidated lipid droplets, and motor defects with systemic treatment of N-acetyl cysteine amide, or reduction of guanine-prone telomere attrition by eicosanoid polyunsaturated fatty acids.
Mitochondrial therapeutics are frequently marketed as supplements and potential therapeutics for neurodegenerative diseases and aging, but results in in vitro and clinical studies are not always in agreement. Further understanding of mitochondrial dysfunctional mechanisms as causative factors and therapeutically viable strategies in neurodegeneration and aging are necessary, and the means to investigate them. This includes the development of patient-derived cellular models such as transdifferentiation models that conserve disease and age-related mtDNA damage, and efficient assay methods to study mitochondrial dysfunction. Additional in vitro and in vivo studies alongside the recent progress of small molecule mitochondrial therapeutics (such as cardiolipin binding SS-31, coenzyme Q10 derivatives, Nrf2 activators omaveloxolone), ex vivo replacement of mitochondria, and infused mitochondrial transfer as organelle replacement strategies are necessary to support the effective development and translation of mitochondrial therapeutics.
In this Research Topic, we welcome Original Research, Reviews, Opinions, Methods manuscript on the following, but not limited to, themes:
• Mitochondrial dysfunction in neurodegenerative diseases and aging
• Mitochondrial therapeutics with potential for application in neurodegenerative diseases and aging
• Cell-based assays analysing mitochondrial function
• Patient-derived stem cell generation and transdifferentiation methods
Progressive neurodegenerative conditions collectively cause over 9 million deaths and 276 million relevant disabilities in a single year. Not unexpectedly the decline of mitochondrial function, responsible for >90% of ATP by oxidative phosphorylation, has been well correlated with cellular pathophysiology, the deterioration of cognitive and motor function, and aging. Mitochondrial dysfunction typically includes reactive oxygen species generation, loss of mtDNA integrity, impaired mitophagy and dynamics. Cellular pathways affected by mitochondrial dysfunction evident by disease and chemical stress models include altered protein synthesis, trafficking and degradation, inflammation, and oxidative damage to nucleic acids, lipids, and proteins, which can lead to cellular dysfunction, telomere attrition, senescence, and death. While unlikely to directly reverse disease progression, therapeutics targeting mitochondrial function have demonstrated potential to mitigate neurodegeneration and age-associated cellular deterioration at the cellular and whole organism level. Encouraging examples include the reduction of ROS, peroxidated lipid droplets, and motor defects with systemic treatment of N-acetyl cysteine amide, or reduction of guanine-prone telomere attrition by eicosanoid polyunsaturated fatty acids.
Mitochondrial therapeutics are frequently marketed as supplements and potential therapeutics for neurodegenerative diseases and aging, but results in in vitro and clinical studies are not always in agreement. Further understanding of mitochondrial dysfunctional mechanisms as causative factors and therapeutically viable strategies in neurodegeneration and aging are necessary, and the means to investigate them. This includes the development of patient-derived cellular models such as transdifferentiation models that conserve disease and age-related mtDNA damage, and efficient assay methods to study mitochondrial dysfunction. Additional in vitro and in vivo studies alongside the recent progress of small molecule mitochondrial therapeutics (such as cardiolipin binding SS-31, coenzyme Q10 derivatives, Nrf2 activators omaveloxolone), ex vivo replacement of mitochondria, and infused mitochondrial transfer as organelle replacement strategies are necessary to support the effective development and translation of mitochondrial therapeutics.
In this Research Topic, we welcome Original Research, Reviews, Opinions, Methods manuscript on the following, but not limited to, themes:
• Mitochondrial dysfunction in neurodegenerative diseases and aging
• Mitochondrial therapeutics with potential for application in neurodegenerative diseases and aging
• Cell-based assays analysing mitochondrial function
• Patient-derived stem cell generation and transdifferentiation methods