Details

Autor(en) / Beteiligte

• Chang, Jui-Chih
• Chang, Huei-Shin
• Chao, Yi-Chun
• Huang, Ching-Shan
• Lin, Chin-Hsien
• Wu, Zhong-Sheng
• Chang, Hui-Ju
• Liu, Chin-San
• Chuang, Chieh-Sen

Titel

Formoterol Acting via β2-Adrenoreceptor Restores Mitochondrial Dysfunction Caused by Parkinson's Disease-Related UQCRC1 Mutation and Improves Mitochondrial Homeostasis Including Dynamic and Transport

Ist Teil von

• Biology (Basel, Switzerland), 2024-04, Vol.13 (4), p.231

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2024

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Formoterol, a β2-adrenergic receptor (β2AR) agonist, shows promise in various diseases, but its effectiveness in Parkinson's disease (PD) is debated, with unclear regulation of mitochondrial homeostasis. This study employed a cell model featuring mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) variants associated with familial parkinsonism, demonstrating mitochondrial dysfunction and dynamic imbalance, exploring the therapeutic effects and underlying mechanisms of formoterol. Results revealed that 24-h formoterol treatment enhanced cell proliferation, viability, and neuroprotection against oxidative stress. Mitochondrial function, encompassing DNA copy number, repatriation, and complex III-linked respiration, was comprehensively restored, along with the dynamic rebalance of fusion/fission events. Formoterol reduced extensive hypertubulation, in contrast to mitophagy, by significantly upregulating protein Drp-1, in contrast to fusion protein Mfn2, mitophagy-related protein Parkin. The upstream mechanism involved the restoration of ERK signaling and the inhibition of Akt overactivity, contingent on the activation of β2-adrenergic receptors. Formoterol additionally aided in segregating healthy mitochondria for distribution and transport, therefore normalizing mitochondrial arrangement in mutant cells. This study provides preliminary evidence that formoterol offers neuroprotection, acting as a mitochondrial dynamic balance regulator, making it a promising therapeutic candidate for PD.