Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits
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TLDR
It is shown that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms contributing to regeneration failure in mature neurons.Abstract:
Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration.read more
Citations
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Mitochondria Localize to Injured Axons to Support Regeneration.
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References
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The Molecular Biology of Axon Guidance
TL;DR: Evidence is accumulating that these mechanisms act simultaneously and in a coordinated manner to direct pathfinding and that they are mediated by mechanistically and evolutionarily conserved ligand-receptor systems.
Journal ArticleDOI
Glial inhibition of CNS axon regeneration
Glenn Yiu,Zhigang He +1 more
TL;DR: The molecular basis of inhibitory molecules in CNS myelin as well as proteoglycans associated with astroglial scarring are evaluated and their contributions to the limitation of long-distance axon repair and other types of structural plasticity are evaluated.
Journal ArticleDOI
Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway
Kevin K. Park,Kai Liu,Yang Hu,Patrice D. Smith,Chen Wang,Bin Cai,Bengang Xu,Lauren Connolly,Ioannis Kramvis,Mustafa Sahin,Zhigang He +10 more
TL;DR: The manipulation of intrinsic growth control pathways as a therapeutic approach to promote axon regeneration after CNS injury is suggested.
Journal ArticleDOI
Mitochondrial dynamics–fusion, fission, movement, and mitophagy–in neurodegenerative diseases
Hsiuchen Chen,David C. Chan +1 more
TL;DR: How mitochondrial dynamics is altered in these neurodegenerative diseases is reviewed and the reciprocal interactions between mitochondrial fusion, fission, transport and mitophagy are discussed.
Journal ArticleDOI
The axonal transport of mitochondria
TL;DR: Why mitochondria move and how they move is reviewed, focusing particularly on recent studies of transport regulation, which implicate control of motor activity by specific cell-signaling pathways, regulation of motor access to transport tracks and static microtubule–mitochondrion linkers.
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