scholarly journals A Recurrent loss-of-function alanyl-tRNA synthetase (AARS ) mutation in patients with charcot-marie-tooth disease type 2N (CMT2N)

2011 ◽  
Vol 33 (1) ◽  
pp. 244-253 ◽  
Author(s):  
Heather M. McLaughlin ◽  
Reiko Sakaguchi ◽  
William Giblin ◽  
Thomas E. Wilson ◽  
Leslie Biesecker ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Disease Type ◽  
Loss Of Function ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals A Recurrent Loss-of-Function Alanyl-tRNA Synthetase (AARS) Mutation in Patients with Charcot-Marie-Tooth Disease Type 2N (CMT2N)

2014 ◽  
Vol 35 (4) ◽  
pp. 512-512 ◽  
Author(s):  
Heather M. McLaughlin ◽  
Reiko Sakaguchi ◽  
William Giblin ◽  
Thomas E. Wilson ◽  
Leslie Biesecker ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Disease Type ◽  
Loss Of Function ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement

2014 ◽  
Vol 54 (11) ◽  
pp. 911-915 ◽  
Author(s):  
Nobuko Kawakami ◽  
Kenichi Komatsu ◽  
Hirofumi Yamashita ◽  
Kengo Uemura ◽  
Nobuyuki Oka ◽  
...  
Keyword(s):  
Respiratory Muscle ◽  
Novel Mutation ◽  
Trna Synthetase ◽  
Disease Type ◽  
Muscle Involvement ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Glycyl tRNA Synthetase Mutations in Charcot-Marie-Tooth Disease Type 2D and Distal Spinal Muscular Atrophy Type V

2003 ◽  
Vol 72 (5) ◽  
pp. 1293-1299 ◽  
Author(s):  
Anthony Antonellis ◽  
Rachel E. Ellsworth ◽  
Nyamkhishig Sambuughin ◽  
Imke Puls ◽  
Annette Abel ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Trna Synthetase ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Spinal Muscular Atrophy Type ◽  
Charcot Marie Tooth Disease ◽  
Type V ◽  
Tooth Disease

scholarly journals SIRT2-knockdown Rescues GARS-induced Charcot-Marie-Tooth Neuropathy

2019 ◽  
Author(s):  
Chao Shen ◽  
Qian Qi ◽  
Yicai Qin ◽  
Dejian Zhou ◽  
Xinyuan Chen ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Nerve Degeneration ◽  
Loss Of Function ◽  
Wild Type ◽  
Partial Loss ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Underlying Mechanisms ◽  
Tooth Disease

AbstractCharcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. Mutations in GARS (GARSCMT2D) show partial loss-of-function features, suggesting that tRNA-charging deficits play a role in disease pathogenesis, but the underlying mechanisms are not fully understood. In this study we report that wild-type GARS tightly binds the NAD+-dependent deacetylase SIRT2 and inhibits its deacetylation activity, resulting in the hyperacetylated α-tubulin, the major substrate of SIRT2. Previous studies showed that acetylation of α-tubulin protects microtubules from mechanical breakage and keep axonal transportation. However, CMT2D mutations in GARS can not inhibit SIRT2 deacetylation, which leads to decrease acetylated α-tubulin and severe axonal transport deficits. Genetic reduction of SIRT2 in the Drosophila model rescues the GARS–induced axonal CMT neuropathy and extends the life span. Our findings demonstrate the pathogenic role of SIRT2-dependent α-tubulin deacetylation in mutant GARS-induced neuropathies and provide new perspectives for targeting SIRT2 as a potential therapy against hereditary axonopathies.

Charcot–Marie–Tooth disease type 2D with a novel glycyl-tRNA synthetase gene (GARS) mutation

2010 ◽  
Vol 257 (7) ◽  
pp. 1202-1204 ◽  
Author(s):  
Ayumi Hamaguchi ◽  
Chiho Ishida ◽  
Kazuo Iwasa ◽  
Akiko Abe ◽  
Masahito Yamada
Keyword(s):  
Trna Synthetase ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Suzan Boutary ◽  
Marie Caillaud ◽  
Mévidette El Madani ◽  
Jean-Michel Vallat ◽  
Julien Loisel-Duwattez ◽  
...  
Keyword(s):  
Mouse Models ◽  
Disease Type ◽  
Major Step ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Protein Levels ◽  
Positive Effects ◽  
Severity Of The Disease ◽  
Tooth Disease

AbstractCharcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease. Pathological studies demonstrated the regeneration of myelinated axons and myelin compaction, one major step in restoring function of myelin sheaths. The normalization of sciatic nerve Krox20, Sox10 and neurofilament levels reflected the regeneration of both myelin and axons. Importantly, the positive effects of siRNA PMP22-SQ NPs lasted for three weeks, and their renewed administration resulted in full functional recovery. Beyond CMT1A, our findings can be considered as a potent therapeutic strategy for inherited peripheral neuropathies. They provide the proof of concept for a new precision medicine based on the normalization of disease gene expression by siRNA.

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