The Role of Axon Transport in Neuroprotection and Regeneration

Shah, Shweta; Goldberg, Jeffrey L

doi:10.1002/dneu.22630

Cited by 17 publications

(7 citation statements)

References 119 publications

(134 reference statements)

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“…7c-d). These phosphorylated forms in the injury experiments may selectively undergo anterograde axonal transport to stimulate MT synthesis and stabilization in regenerating axons [38].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation sites of microtubule-associated protein 1B (MAP 1B) are involved in axon growth and regeneration

et al. 2019

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The growth cone is a specialized structure that forms at the tip of extending axons in developing and regenerating neurons. This structure is essential for accurate synaptogenesis at developmental stages, and is also involved in plasticity-dependent synaptogenesis and axon regeneration in the mature brain. Thus, understanding the molecular mechanisms utilized by growth cones is indispensable to understanding neuronal network formation and rearrangement. Phosphorylation is the most important and commonly utilized protein modification in signal transduction. We previously identified microtubule-associated protein 1B (MAP 1B) as the most frequently phosphorylated protein among ~ 1200 phosphorylated proteins. MAP 1B has more than 10 phosphorylation sites that were present more than 50 times among these 1200 proteins. Here, we produced phospho-specific antibodies against phosphorylated serines at positions 25 and 1201 of MAP 1B that specifically recognize growing axons both in cultured neurons and in vivo in various regions of the embryonic brain. Following sciatic nerve injury, immunoreactivity with each antibody increased compared to the sham operated group. Experiments with transected and sutured nerves revealed that regenerating axons were specifically recognized by these antibodies. These results suggest that these MAP 1B phosphorylation sites are specifically involved in axon growth and that phospho-specific antibodies against MAP 1B are useful markers of growing/regenerating axons.

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“…7c-d). These phosphorylated forms in the injury experiments may selectively undergo anterograde axonal transport to stimulate MT synthesis and stabilization in regenerating axons [38].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation sites of microtubule-associated protein 1B (MAP 1B) are involved in axon growth and regeneration

et al. 2019

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“…Early studies in non-human primates found that elevations in IOP and reduced OPP were associated with obstruction of axonal transport in the ONH [ 19 , 33 , 52 , 53 , 54 ]. At that time, the IOP rise was mostly acute, and in some cases reaching values above 60 mm Hg or even >100 mm Hg, leading to an expressive decrease in perfusion pressure [ 19 , 33 , 52 , 55 , 56 , 57 ].…”

Section: Axonal Damage In Glaucomamentioning

confidence: 99%

The Role of Axonal Transport in Glaucoma

Dias

Luo

Ribas

et al. 2022

IJMS

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Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs) and leads to progressive vision loss. The first pathological signs can be seen at the optic nerve head (ONH), the structure where RGC axons leave the retina to compose the optic nerve. Besides damage of the axonal cytoskeleton, axonal transport deficits at the ONH have been described as an important feature of glaucoma. Axonal transport is essential for proper neuronal function, including transport of organelles, synaptic components, vesicles, and neurotrophic factors. Impairment of axonal transport has been related to several neurodegenerative conditions. Studies on axonal transport in glaucoma include analysis in different animal models and in humans, and indicate that its failure happens mainly in the ONH and early in disease progression, preceding axonal and somal degeneration. Thus, a better understanding of the role of axonal transport in glaucoma is not only pivotal to decipher disease mechanisms but could also enable early therapies that might prevent irreversible neuronal damage at an early time point. In this review we present the current evidence of axonal transport impairment in glaucomatous neurodegeneration and summarize the methods employed to evaluate transport in this disease.

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“…In optic neuropathies, the initial injury occurs in the axons of RGCs, and axonopathy precedes death of the soma [25]. In glaucoma, elevated IOP leads to impaired axonal transport, including transport of brain-derived neurotrophic factor (BDNF) [26], which then lead to somatic degeneration [14,27]. In AION animal model, massive axonal degeneration occurs within 7 days after onset [28•], which precedes the first peak of RGC death at day 10 [29].…”

Section: Axonopathy Precedes Rgc Death In Optic Neuropathiesmentioning

confidence: 99%

Optic Nerve Regeneration: Considerations on Treatment of Acute Optic Neuropathy and End-Stage Disease

Mesentier-Louro

Liao

2019

Curr Ophthalmol Rep

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Purpose of Review Acute and chronic optic neuropathies lead to irreversible vision loss, prompting considerations of regenerative therapy. Th e insult commonly occurs primarily in the anterior optic nerve, which leads to degeneration of retinal ganglion cells (RGCs) and their axons and loss of oligodendrocytes. We review important aspects of optic nerve regeneration and animal models of disease. Recent Findings Preclinical studies in animals showed that approaches that improve RGC survival and axon regeneration include neurotrophic factor delivery, genetic manipulation, visual stimulation, and cell therapies, but impact on glia must be also considered. While intravitreal delivery of molecules has been most commonly used, direct targeting of the optic nerve should be considered. Summary Treatment can differ if targeting acute or subacute vs. chronic optic neuropathies, depending on whether most RGC axons and somata are still present and salvageable, or if somata and axons are gone and need to be replaced. Combined neuron-and glia-directed treatments may lead to more successful vision restoration.

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The Role of Axon Transport in Neuroprotection and Regeneration

Cited by 17 publications

References 119 publications

Phosphorylation sites of microtubule-associated protein 1B (MAP 1B) are involved in axon growth and regeneration

Phosphorylation sites of microtubule-associated protein 1B (MAP 1B) are involved in axon growth and regeneration

The Role of Axonal Transport in Glaucoma

Optic Nerve Regeneration: Considerations on Treatment of Acute Optic Neuropathy and End-Stage Disease

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