(S)-ZJM-289, a nitric oxide-releasing derivative of 3-n-butylphthalide, protects against ischemic neuronal injury by attenuating mitochondrial dysfunction and associated cell death

2012 ◽  
Vol 60 (2) ◽  
pp. 134-144 ◽  
Author(s):  
Qian Zhao ◽  
Chao Zhang ◽  
Xuliang Wang ◽  
Li Chen ◽  
Hui Ji ◽  
...  
2004 ◽  
Vol 20 (7) ◽  
pp. 1713-1726 ◽  
Author(s):  
Olivier Baud ◽  
Jianrong Li ◽  
Yumin Zhang ◽  
Rachael L. Neve ◽  
Joseph J. Volpe ◽  
...  

2019 ◽  
Vol 218 (6) ◽  
pp. 1891-1907 ◽  
Author(s):  
Yanrong Zheng ◽  
Xiangnan Zhang ◽  
Xiaoli Wu ◽  
Lei Jiang ◽  
Anil Ahsan ◽  
...  

Mitophagy protects against ischemic neuronal injury by eliminating damaged mitochondria, but it is unclear how mitochondria in distal axons are cleared. We find that oxygen and glucose deprivation-reperfusion reduces mitochondrial content in both cell bodies and axons. Axonal mitochondria elimination was not abolished in Atg7fl/fl;nes-Cre neurons, suggesting the absence of direct mitophagy in axons. Instead, axonal mitochondria were enwrapped by autophagosomes in soma and axon-derived mitochondria prioritized for elimination by autophagy. Intriguingly, axonal mitochondria showed prompt loss of anterograde motility but increased retrograde movement upon reperfusion. Anchoring of axonal mitochondria by syntaphilin blocked neuronal mitophagy and aggravated injury. Conversely, induced binding of mitochondria to dynein reinforced retrograde transport and enhanced mitophagy to prevent mitochondrial dysfunction and attenuate neuronal injury. Therefore, we reveal somatic autophagy of axonal mitochondria in ischemic neurons and establish a direct link of retrograde mitochondrial movement with mitophagy. Our findings may provide a new concept for reducing ischemic neuronal injury by correcting mitochondrial motility.


Author(s):  
Xiuyu Wu ◽  
Ximin Hu ◽  
Qi Zhang ◽  
Fengxia Liu ◽  
Kun Xiong

: Ischemic neuronal injury results from a complex series of pathophysiological events, including oxidative, excitotoxicity, inflammation and nitrative stress. Consequently, many of these events can induce cell death, including necrosis (unregulated cell death) and apoptosis (a type of regulated cell death). These are long-established paradigms to which newly discovered regulated cell death processes have been added, such as necroptosis (a regulated form of necrosis) and autophagy-dependent cell death. Moreover, many researchers have targeted products associated with Chinese herbal medicine at regulated pathways for the treatment of ischemic neuronal injury. In East Asia, these drugs have been known for centuries to protect and improve the nervous system. Herbal extracts, especially those used in Chinese herbal medicine, have emerged as new pharmaceuticals for the treatment of ischemic neuronal injury. Here, we review the evidence from preclinical studies investigating the neuroprotective properties and therapeutic application of Chinese herbal medicines (Chinese herbal monomer, extract, and medicinal compounds) and highlight the potential mechanisms underlying their therapeutic effects via targeting different regulated cell death pathways. Notably, many herbs have been shown to target multiple mechanisms of regulated cell death and, in combination, may exert synergistic effects on signaling pathways, thereby attenuating multiple aspects of ischemic pathology. In this review, we summarize a general regulated pathway of cell death as a target for novel natural herbal regimens against ischemic neuronal injury.


Neuron ◽  
2004 ◽  
Vol 41 (3) ◽  
pp. 351-365 ◽  
Author(s):  
Ella Bossy-Wetzel ◽  
Maria V Talantova ◽  
Wilson D Lee ◽  
Marion N Schölzke ◽  
Anne Harrop ◽  
...  

2009 ◽  
Vol 385 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Kiyoshi Kikuchi ◽  
Ko-ichi Kawahara ◽  
Kamal Krishna Biswas ◽  
Takashi Ito ◽  
Salunya Tancharoen ◽  
...  

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