scholarly journals Impaired Mitochondrial Mobility in Charcot-Marie-Tooth Disease

2020 ◽  
Author(s):  
Cara Schiavon ◽  
Uri Manor
Keyword(s):  
Clinical Manifestations ◽  
Underlying Mechanism ◽  
The Body ◽  
Charcot Marie Tooth ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Challenges And Opportunities ◽  
Axonal Cmt ◽  
Trafficking Defects

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, defined by progressive deterioration of the peripheral nerves. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility. This suggests that trafficking defects may be a common underlying mechanism in CMT. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the challenges and opportunities to this “impaired mobility” model of the disease.

scholarly journals Impaired Mitochondrial Mobility in Charcot-Marie-Tooth Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Cara R. Schiavon ◽  
Gerald S. Shadel ◽  
Uri Manor
Keyword(s):  
Clinical Manifestations ◽  
Underlying Disease ◽  
Mobility Model ◽  
The Body ◽  
Charcot Marie Tooth ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Organelle Trafficking ◽  
Axonal Cmt ◽  
Trafficking Defects

Charcot-Marie-Tooth (CMT) disease is a progressive, peripheral neuropathy and the most commonly inherited neurological disorder. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility, suggesting that organelle trafficking defects may be a common underlying disease mechanism. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the conceptional challenges and potential experimental and therapeutic opportunities presented by this “impaired mobility” model of the disease.

Normal role of the low‐molecular‐weight neurofilament protein in mitochondrial dynamics and disruption in Charcot‐Marie‐Tooth disease

2011 ◽  
Vol 26 (3) ◽  
pp. 1194-1203 ◽  
Author(s):  
Benoit J. Gentil ◽  
Sandra Minotti ◽  
Madeleine Beange ◽  
Robert H. Baloh ◽  
Jean‐Pierre Julien ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Mitochondrial Dynamics ◽  
Low Molecular Weight ◽  
Neurofilament Protein ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

SIMPLEmutations in Charcot-Marie-Tooth disease and the potential role of its protein product in protein degradation

2005 ◽  
Vol 25 (4) ◽  
pp. 372-383 ◽  
Author(s):  
Gulam Mustafa Saifi ◽  
Kinga Szigeti ◽  
Wojciech Wiszniewski ◽  
Michael E. Shy ◽  
Karen Krajewski ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Potential Role ◽  
Protein Product ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Congenital Bilateral Vocal Cord Paralysis and the Role of Glycine

2005 ◽  
Vol 114 (6) ◽  
pp. 494-498 ◽  
Author(s):  
Robert G. Berkowitz ◽  
Qi-Jian Sun ◽  
Paul M. Pilowsky
Keyword(s):  
Vocal Cord ◽  
Vocal Cord Paralysis ◽  
Clinical Manifestations ◽  
Underlying Mechanism ◽  
Sprague Dawley ◽  
Bilateral Vocal Cord Paralysis ◽  
Sprague Dawley Rats ◽  
Motoneuron Activity ◽  
Made In

Objectives: We sought to modify normal laryngeal constrictor (LC) motoneuron activity to induce a pattern of aberrant LC muscle function that may serve as a model of congenital bilateral vocal cord paralysis. Methods: Single unit extracellular recordings of functionally identified LC motoneurons were made in anesthetized Sprague-Dawley rats, and the response to both intravenous and iontophoretic application of the glycine antagonist strychnine was studied. Results: The postinspiratory firing pattern of LC motoneurons became inspiratory after intravenous injection of strychnine (4 of 5 rats), but no change was recorded in response to strychnine iontophoresis (7 of 8 rats). Conclusions: Blockade of glycinergic inhibitory neurotransmission by strychnine, acting above the level of the LC motoneuron, causes LC motoneurons to fire during inspiration rather than after inspiration. This observation suggests that impaired glycine neurotransmission may be an underlying mechanism that explains the clinical manifestations of congenital bilateral vocal cord paralysis.

scholarly journals A case of X-linked Charcot-Marie-tooth disease type 1 manifesting as recurrent alternating hemiplegia with transient cerebral white matter lesions

2021 ◽  
Vol 23 (2) ◽  
pp. 130-133
Author(s):  
Minsung Kang ◽  
Sun-Jae Hwang ◽  
Jin-Hong Shin ◽  
Dae-Seong Kim
Keyword(s):  
Nervous System ◽  
Clinical Manifestations ◽  
White Matter Lesions ◽  
Disease Type ◽  
Cerebral White Matter ◽  
Hereditary Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

X-linked Charcot Marie Tooth disease type 1 (CMTX1) is a clinically heterogenous X-linked hereditary neuropathy caused by mutation of the gene encoding gap junction beta 1 protein (GJB1). Typical clinical manifestations of CMTX1 are progressive weakness or sensory disturbance due to peripheral neuropathy. However, there have been some CMTX1 cases with accompanying central nervous system (CNS) manifestations. We report the case of a genetically confirmed CMTX1 patient who presented recurrent transient CNS symptoms without any symptom or sign of peripheral nervous system involvement.

scholarly journals Transient, Recurrent Central Nervous System Clinical Manifestations of X-Linked Charcot-Marie-Tooth Disease Presenting with Very Long Latency Periods between Episodes: Is Prolonged Sun Exposure a Provoking Factor?

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Andria Tziakouri ◽  
Konstantinos Natsiopoulos ◽  
Kleopas A. Kleopa ◽  
Costas Michaelides
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prolonged Exposure ◽  
Clinical Manifestations ◽  
Sun Exposure ◽  
Foot Deformities ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Long Latency ◽  
Tooth Disease

Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders affecting the peripheral nervous system. The common clinical manifestations of the disease are distal muscle weakness and atrophy, often associated with a characteristic steppage gait and foot deformities. Transient acute and recurrent or chronic central nervous system manifestations, predominantly, dysarthria, dysphagia, motor weakness, and ataxia, have been recognized as a feature of the X-linked type 1 of CMT (CMTX1). The CNS symptoms occur typically in young age and often precede the clinical manifestation of the polyneuropathy. Several predisposing factors such as exercise, fever, and returning from areas of high altitude have been described as triggers of the CNS symptoms; however, in many cases, a substantial cause remains undetermined. In this report, we describe a patient with three attacks of transient CNS deficits at the ages of 11, 21, and 38 years, respectively, which were also accompanied by transient white matter abnormalities on MRI. Two of the attacks occurred after prolonged exposure to sunlight. In our knowledge, this is the first documented case with such long latency periods between CNS attacks as well as the only report describing intense sun exposure as a possible provoking factor.

scholarly journals Held Up in Traffic—Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Ronja Markworth ◽  
Mathias Bähr ◽  
Katja Burk
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Intracellular Transport ◽  
Early Adulthood ◽  
Sensory Neuropathy ◽  
Common Denominator ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Trafficking Defects ◽  
Tooth Disease

Charcot-Marie-Tooth disease (CMT), also known as motor and sensory neuropathy, describes a clinically and genetically heterogenous group of disorders affecting the peripheral nervous system. CMT typically arises in early adulthood and is manifested by progressive loss of motor and sensory functions; however, the mechanisms leading to the pathogenesis are not fully understood. In this review, we discuss disrupted intracellular transport as a common denominator in the pathogenesis of different CMT subtypes. Intracellular transport via the endosomal system is essential for the delivery of lipids, proteins, and organelles bidirectionally to synapses and the soma. As neurons of the peripheral nervous system are amongst the longest neurons in the human body, they are particularly susceptible to damage of the intracellular transport system, leading to a loss in axonal integrity and neuronal death. Interestingly, defects in intracellular transport, both in neurons and Schwann cells, have been found to provoke disease. This review explains the mechanisms of trafficking and subsequently summarizes and discusses the latest findings on how defects in trafficking lead to CMT. A deeper understanding of intracellular trafficking defects in CMT will expand our understanding of CMT pathogenesis and will provide novel approaches for therapeutic treatments.

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