Mitochondrial Behavior in Axon Degeneration and Regeneration

Wang, Biyao; Huang, Ming-Jer; Shang, Dehao; Xu, Yan; Zhao, Baohong; Zhang, Xinwen

doi:10.3389/fnagi.2021.650038

Cited by 46 publications

(41 citation statements)

References 210 publications

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“…Despite rapid progress in understanding and manipulating axon growth postinjury, the impact of age on axon growth and regeneration in the CNS has not been characterized. Mitochondria are vital to axon growth and regeneration [ 29 , 30 ]. These organelles are known to decrease in efficacy and functionality with age and after SCI, representing a point where aging and SCI intersect.…”

Section: Discussionmentioning

confidence: 99%

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Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Sutherland

Sefiani

Horvat

et al. 2021

Cells

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The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.

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Section: Discussionmentioning

confidence: 99%

“…Mitochondria play important roles in normal aging [ 12 ], axon growth [ 25 , 26 , 27 , 28 , 29 , 30 ], and the progression of SCI [ 31 , 32 , 33 ]. Significantly, mitochondrial dysfunctions and detrimental oxidative stress are associated with both normal aging and central nervous system (CNS) trauma.…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Sutherland

Sefiani

Horvat

et al. 2021

Cells

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“…The presence of axonal spheroids and perikaryal accumulations/aggregations (comprising the neuronal intermediate filament proteins) have been observed in sporadic cases of ALS as well as in mutant SOD1 patients, likely interfering with axonal transport [46]. Mitochondrial dysfunction occurs at an early stage of axon degeneration [47]. ALS-associated mitochondrial bioenergetic deficits are evident in the most common ALS-causing mutation, C9orf72 [48].…”

Section: Glia Neuroinflammation and Motor Neuron Mitochondriamentioning

confidence: 99%

The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS

Obrador

Palmer

López-Blanch

et al. 2021

IJMS

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Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. It is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and paralysis. ALS is incurable and has a bleak prognosis, with median survival of 3–5 years after the initial symptomatology. In ALS, motor neurons gradually degenerate and die. Many features of mitochondrial dysfunction are manifested in neurodegenerative diseases, including ALS. Mitochondria have shown to be an early target in ALS pathophysiology and contribute to disease progression. Disruption of their axonal transport, excessive generation of reactive oxygen species, disruption of the mitochondrial structure, dynamics, mitophagy, energy production, calcium buffering and apoptotic triggering have all been directly involved in disease pathogenesis and extensively reported in ALS patients and animal model systems. Alterations in energy production by motor neurons, which severely limit their survival capacity, are tightly linked to the redox status and mitochondria. The present review focuses on this link. Placing oxidative stress as a main pathophysiological mechanism, the molecular interactions and metabolic flows involved are analyzed. This leads to discussing potential therapeutic approaches targeting mitochondrial biology to slow disease progression.

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“…Therefore, the spinal cord is highly susceptible to oxidative damage. The significance of ROS and lipid peroxidation during SCI has been validated by numerous experimental and clinical studies [17][18][19][20][21][22], and therapeutic strategies targeting oxidative stress pathways are increasingly showing promising applications.…”

Section: Introductionmentioning

confidence: 99%

Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury

Lin

Xiong

et al. 2021

Oxidative Medicine and Cellular Longevity

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Spinal cord injury (SCI) is one of the most incapacitating neurological disorders. It involves complex pathological processes that include a primary injury and a secondary injury phase, or a delayed stage, which follows the primary injury and contributes to the aggravation of the SCI pathology. Oxidative stress, a key pathophysiological event after SCI, contributes to a cascade of inflammation, excitotoxicity, neuronal and glial apoptosis, and other processes during the secondary injury phase. In recent years, increasing evidence has demonstrated that sirtuins are protective toward the pathological process of SCI through a variety of antioxidant mechanisms. Notably, strategies that modulate the expression of sirtuins exert beneficial effects in cellular and animal models of SCI. Given the significance and novelty of sirtuins, we summarize the oxidative stress processes that occur in SCI and discuss the antioxidant effects of sirtuins in SCI. We also highlight the potential of targeting sirtuins for the treatment of SCI.

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Mitochondrial Behavior in Axon Degeneration and Regeneration

Cited by 46 publications

References 210 publications

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS

Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury

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