ZLN005, a PGC-1α agonist, delays photoreceptor degeneration by enhancing mitochondrial biogenesis in a murine model of retinitis pigmentosa DOI Creative Commons

Chaojun Hu,

Chengda Ren, Yan Wu

и другие.

Neuropharmacology, Год журнала: 2025, Номер 269, С. 110361 - 110361

Опубликована: Фев. 12, 2025

Retinitis pigmentosa (RP) is a hereditary neurodegenerative disease characterized by the degeneration of photoreceptors caused mutations in various genes. Increasing evidence suggests that mitochondrial biogenesis plays critical role many diseases. This study investigated rd1 mice, widely recognized model RP. Male C57BL/6 mice and age-matched were used for vivo experiments, while H2O2 was employed on 661w cells to establish an vitro model. Our findings revealed regulatory PGC-1α/NRF-1/TFAM pathway significantly downregulated mice. Treatment with ZLN005, PGC-1α agonist, markedly improved visual function alleviated thinning retinal outer nuclear layer. Additionally, ZLN005 enhanced restored photoreceptors. Further analysis confirmed rescued photoreceptor promoting through pathway. In summary, our results highlight progression offers potential strategy delay RP maintaining could be combined existing therapies improving treatment outcomes synergistic pathways.

Язык: Английский

The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria DOI Creative Commons

Wanting Xu,

Lei Dong, Jiyan Dai

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Янв. 12, 2025

Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through continuous accumulation misfolded proteins and damaged organelles. This review delineates roles two complementary synergistic degradation systems, ubiquitin–proteasome system (UPS) autophagy-lysosome system, in organelles for intracellular recycling. We emphasize interconnected decision-making processes systems maintaining homeostasis, such as biophysical state substrates, receptor oligomerization potentials (e.g., p62), compartmentalization capacities membrane structures). Mitochondria, hubs respiration metabolism, are implicated tumorigenesis. In subsequent sections, we thoroughly examine mechanisms mitochondrial quality control (MQC) preserving human cells. Notably, explored relationships between dynamics (fusion fission) various MQC processes—including UPS, proteases, mitophagy—in context repair pathways. Finally, assessed potential targeting (including molecular chaperones, dynamics, mitophagy biogenesis) therapeutic strategies. Understanding underlying may offer novel insights future therapies. highlights UPS degrading proteins, emphasizing substrate states, oligomerization, homeostasis. Innovatively links coordination to examining interplay these pathways varying degrees damage.

Язык: Английский

Процитировано

2
ZLN005, a PGC-1α agonist, delays photoreceptor degeneration by enhancing mitochondrial biogenesis in a murine model of retinitis pigmentosa DOI Creative Commons

Chaojun Hu,

Chengda Ren, Yan Wu

и другие.

Neuropharmacology, Год журнала: 2025, Номер 269, С. 110361 - 110361

Опубликована: Фев. 12, 2025

Retinitis pigmentosa (RP) is a hereditary neurodegenerative disease characterized by the degeneration of photoreceptors caused mutations in various genes. Increasing evidence suggests that mitochondrial biogenesis plays critical role many diseases. This study investigated rd1 mice, widely recognized model RP. Male C57BL/6 mice and age-matched were used for vivo experiments, while H2O2 was employed on 661w cells to establish an vitro model. Our findings revealed regulatory PGC-1α/NRF-1/TFAM pathway significantly downregulated mice. Treatment with ZLN005, PGC-1α agonist, markedly improved visual function alleviated thinning retinal outer nuclear layer. Additionally, ZLN005 enhanced restored photoreceptors. Further analysis confirmed rescued photoreceptor promoting through pathway. In summary, our results highlight progression offers potential strategy delay RP maintaining could be combined existing therapies improving treatment outcomes synergistic pathways.

Язык: Английский

Процитировано

0