Defective axonal transport: A common pathological mechanism in inherited and acquired peripheral neuropathies

Prior, Robert; Helleputte, Lawrence Van; Benoy, Veronick; Bosch, Ludo Van Den

doi:10.1016/j.nbd.2017.02.009

Cited by 97 publications

(71 citation statements)

References 226 publications

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“…This is called axonal transport. This transport can also get disrupted due to any injury, genetic disorder, or disease, which may lead to neuropathic pain [41]. Lastly, biochemical processes such as release of cytokines and other inflammatory molecules are also involved in generation of inflammatory pain.…”

Section: Discussionmentioning

confidence: 99%

Using Bifurcation Theory for Exploring Pain

Verma

Kienle

Flockerzi

et al. 2019

Preprint

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Pain is a common sensation which inescapably arises due to injuries, as well as, various diseases and disorders. However, for the same intensity of disturbance arising due to the forgoing causes, the threshold for pain sensation and perception varies among individuals. Here, we present a computational approach using bifurcation theory to understand how the pain sensation threshold varies and how it can be controlled, the threshold being quantified by the electrical activity of a pain-sensing neuron. To this end, we explored the bifurcations arising from a mathematical model representing the dynamics of this neuron. Our findings indicate that the bifurcation points are sensitive to specific model parameters. This demonstrates that the pain sensation threshold can change as shown in experimental studies found in literature. Further investigation using our bifurcation approach coupled with experimental studies can facilitate rigorous understanding of pain response mechanism and provide strategies to control the pain sensation threshold.

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Section: Discussionmentioning

confidence: 99%

Using Bifurcation Theory for Exploring Pain

Verma

Kienle

Flockerzi

et al. 2019

Preprint

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“…Deficits in axonal transport contribute to many different genetic neuropathies (Prior et al, 2017;Beijer et al, 2019), and its early involvement in disease may be a common driver in peripheral nerve selectivity typical of many forms of CMT2. Indeed, disruption of long-range trafficking has been identified in sensory neurons cultured from CMT2D DRG (Benoy et al, 2018;Mo et al, 2018).…”

Section: Long-range Transport Is Not Universally Impaired In Cmt2d Sementioning

confidence: 99%

Altered sensory neuron development in CMT2D mice is site-specific and linked to increased GlyRS levels

Sleigh

Mech

Aktar

et al. 2020

Preprint

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Dominant, missense mutations in the widely and constitutively expressed GARS1 gene cause a peripheral neuropathy that usually begins in adolescence and principally impacts the upper limbs. Caused by a toxic gain-of-function in the encoded glycyl-tRNA synthetase (GlyRS) enzyme, the neuropathology appears to be independent of the canonical role of GlyRS in aminoacylation. Patients display progressive, life-long weakness and wasting of muscles in hands followed by feet, with frequently associated deficits in sensation. When dysfunction is observed in motor and sensory nerves, there is a diagnosis of Charcot-Marie-Tooth disease type 2D (CMT2D), or distal hereditary motor neuropathy type V if the symptoms are purely motor. The cause of this varied sensory involvement remains unresolved, as are the pathomechanisms underlying the selective neurodegeneration characteristic of the disease. We have previously identified in CMT2D mice that neuropathy-causing Gars mutations perturb sensory neuron fate and permit mutant GlyRS to aberrantly interact with neurotrophin receptors (Trks). Here, we extend this work by interrogating further the anatomy and function of the CMT2D sensory nervous system in mutant Gars mice, obtaining several key results: 1) sensory pathology is restricted to neurons innervating the hindlimbs; 2) perturbation of sensory development is not common in mouse models of neuromuscular disease; 3) in vitro axonal transport of signalling endosomes is not impaired in afferent neurons of all CMT2D mouse models; and 4) Gars expression is selectively elevated in a subset of sensory neurons and linked to sensory developmental defects. These findings highlight the importance of comparative neurological assessment in mouse models of disease and shed light on key proposed neuropathogenic mechanisms in GARS1-linked neuropathy.

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“…In vibration-associated neuropathies, conceivable target structures could be peripheral sensory receptors, large or thin myelinated nerve fibers, and small-caliber, nonmyelinated C fibers. Pathological studies by cutaneous biopsy have demonstrated demyelinating neuropathy in the digital nerves of individuals with HAVS [5][6][7][8].…”

Section: Differential Diagnosis In the Whsmentioning

confidence: 99%

Working Hand Syndrome: A New Definition of Nonclassified Polyneuropathy Condition

Özdemir¹

2019

Demystifying Polyneuropathy - Recent Advances and New Directions

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The aim of this chapter was to define an unexplained nonclassified polyneuropathy condition as a new neurological disease. This new diagnosis of occupationrelated polyneuropathy has been named as "working hand syndrome (WHS)." This study collected and compared clinical and electrophysiological analyses data from healthy controls, WHS patients, carpal tunnel syndrome (CTS) patients, and polyneuropathy patients. The WHS patients presented to the clinic with pain, numbness, tingling, and burning sensations in their hands that increased significantly during rest and nighttime. However, there was no weakness in the muscles, and the deep tendon reflexes were normal in this disease. The patients had all been working in physically demanding jobs requiring the use of their hands/arms for at least 1 year, but no vibrating tools were used by the patients. All of the cases were men. I suppose that overload caused by an action repeated chronically by the hand/arm may impair the sensory nerves in mentioned hand/arm. In patients with these complaints, for a definitive diagnosis, similar diseases must be excluded. Nonetheless, the specific electrophysiological finding that the sural nerves are normal on the lower sides, as well as the occurrence of sensory axonal polyneuropathy in the sensory nerves without a significant effect on velocity and latency in the work-ups of the upper extremity are enough to make a diagnosis.

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Defective axonal transport: A common pathological mechanism in inherited and acquired peripheral neuropathies

Cited by 97 publications

References 226 publications

Using Bifurcation Theory for Exploring Pain

Using Bifurcation Theory for Exploring Pain

Altered sensory neuron development in CMT2D mice is site-specific and linked to increased GlyRS levels

Working Hand Syndrome: A New Definition of Nonclassified Polyneuropathy Condition

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