Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Technology Enterprise (BRITE), North Carolina Central University, Durham, North Carolina.
Department of Neurology, General Hospital of Ningxia Medical University, Ningxia Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, PR China.
J Neurosci Res. 2017 Oct;95(10):2025-2029. doi: 10.1002/jnr.24042. Epub 2017 Mar 16.
Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in mitochondrial dynamic imbalance, free radical production, calcium accumulation, intrinsic cell death pathway activation and eventually cell death. Therefore, preserving or promoting mitochondrial function is a potential therapeutic target for the treatment of neurodegenerative disorders. Mitochondrial biogenesis is a process by which new mitochondria are produced from existing mitochondria. This biogenesis process is regulated by Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1alpha (PGC-1α). Once being activated by either phosphorylation or de-acetylation, PGC-1α activates nuclear respiratory factor 1 and 2 (NRF1 and NRF2), and subsequently mitochondrial transcription factor A (Tfam). The activation of this PGC-1α - NRF -Tfam pathway leads to synthesis of mitochondrial DNA and proteins and generation of new mitochondria. © 2017 Wiley Periodicals, Inc.
线粒体在能量产生、钙稳态、细胞存活和死亡中发挥着关键作用。神经退行性疾病等不利刺激可能导致线粒体动态失衡、自由基产生、钙积累、内在细胞死亡途径激活，最终导致细胞死亡。因此，保留或促进线粒体功能是治疗神经退行性疾病的潜在治疗靶点。线粒体生物发生是指新的线粒体从现有线粒体中产生的过程。这个生物发生过程受到过氧化物酶体增殖物激活受体-γ（PPARγ）共激活因子-1α（PGC-1α）的调节。PGC-1α 一旦被磷酸化或去乙酰化激活，就会激活核呼吸因子 1 和 2（NRF1 和 NRF2），并随后激活线粒体转录因子 A（Tfam）。这个 PGC-1α-NRF-Tfam 通路的激活导致线粒体 DNA 和蛋白质的合成以及新线粒体的产生。©2017 年 Wiley 期刊，Inc.
