scholarly journals Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice

2013 ◽  
Vol 210 (4) ◽  
pp. 821-838 ◽  
Author(s):  
Maurizio D’Antonio ◽  
Nicolò Musner ◽  
Cristina Scapin ◽  
Daniela Ungaro ◽  
Ubaldo Del Carro ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Therapeutic Strategy ◽  
Terminal Differentiation ◽  
Motor Deficit ◽  
Demyelinating Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Unfolded Protein ◽  
Protein Response ◽  
Tooth Disease

P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

MicroRNAs as Biomarkers of Charcot-Marie-Tooth Disease Type 1A

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012266
Author(s):  
Hongge Wang ◽  
Matthew Davison ◽  
Kathryn Wang ◽  
Tai-he Xia ◽  
Katherine M. Call ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Motor Nerve ◽  
Disease Type ◽  
Class Iii ◽  
Protein Biomarkers ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Compound Muscle Action Potentials ◽  
Tooth Disease

Objective:To determine if microRNA’s (miR) are elevated in the plasma of individuals affected by the inherited peripheral neuropathy Charcot-Marie-Tooth Disease, type 1A (CMT1A), miR profiling was employed to compare control and CMT1A plasma.Methods:We performed a screen of CMT1A and control plasma samples to identify miRs that are elevated in CMT1A using next generation sequencing, followed by validation of selected miRs by quantitative PCR, and correlation with protein biomarkers and clinical data: Rash-modified CMT Examination and Neuropathy Scores (CMTES-R and CMTNS-R), ulnar compound muscle action potentials (CMAP), and motor nerve conduction velocities (MNCV).Results:After an initial pilot screen, a broader screen confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerve. Comparison to other candidate biomarkers for CMT1A (e.g. Neurofilament L, NfL) measured on the same sample set shows a comparable elevation of several miRs (e.g. miR133a, -206, -223) and ability to discriminate cases from controls. NfL levels were most highly correlated with miR133a. In addition, the putative Schwann cell miRs (e.g. miR223, -199a, -328, -409, and -431) correlate with the recently described TMPRSS5 protein biomarker that is most highly expressed in Schwann cells and also elevated in CMT1A plasma.Conclusions:These studies identify a set of miRs that are candidate biomarkers for clinical trials in CMT1A. Some of the miRs may reflect Schwann cell processes that underlie the pathogenesis of the disease.Classification of Evidence:This study provides Class III evidence that a set of plasma miRs are elevated in patients with CMT1A.

Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot–Marie–Tooth disease type 1A

2006 ◽  
Vol 33 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Roberto Massa ◽  
Camilla Palumbo ◽  
Tiziana Cavallaro ◽  
Maria Beatrice Panico ◽  
Roberto Bei ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Case Report: Oculomotor Palsy With Cyclic Spasms in a Patient With Charcot-Marie-Tooth Disease Type 1

2021 ◽  
Vol 1 ◽  
Author(s):  
Konrad P. Weber ◽  
Christopher J. Bockisch ◽  
Klara Landau
Keyword(s):  
Sensory Neuropathy ◽  
Rare Condition ◽  
Disease Type ◽  
Oculomotor Nerve ◽  
Oculomotor Palsy ◽  
Demyelinating Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Oculomotor palsy with cyclic spasms is an extremely rare condition whose exact pathophysiology remains a mystery. We followed a boy from the onset of symptoms at the age of ten months until 15 years and documented the case with video oculography. In addition, he was diagnosed with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease type 1). Although a pure coincidence cannot be ruled out, it is conceivable that the underlying demyelinating neuropathy of this patient rendered the oculomotor nerve more susceptible to damage.

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