Baclofen-Naltrexone-Sorbitol for Charcot-Marie-Tooth DiseaseBaclofen-Naltrexone-Sorbitol for Charcot-Marie-Tooth Disease

Combining three familiar drugs that treat other conditions may help patients with Charcot-Marie-Tooth type 1A disease (CMT1A), a new proof-of-concept study suggests. Reuters Health Information
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Neurology & Neurosurgery News Source Type: news

Related Links:

Motoneurons are particularly sensitive to mutations in mitofusin-2 (MFN2) that cause the neurological disorder Charcot-Marie-Tooth disease type 2A (CMT2A). MFN2 is a mitochondrial outer membrane protein that, together with its homologue MFN1, fuses mitochondria in most tissues. In this issue of the JCI, Zhou and colleagues show that increasing MFN1 expression in neurons can curtail neurological defects in a CMT2A mouse model. These results show that the ratio of MFN1 to MFN2 can explain the tissue specificity of CMT2A and indicate that augmentation of MFN1 in the nervous system has potential as a possible therapeutic strategy for CMT2A.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Mitofusin-2 (MFN2) is a mitochondrial outer-membrane protein that plays a pivotal role in mitochondrial dynamics in most tissues, yet mutations in MFN2, which cause Charcot-Marie-Tooth disease type 2A (CMT2A), primarily affect the nervous system. We generated a transgenic mouse model of CMT2A that developed severe early onset vision loss and neurological deficits, axonal degeneration without cell body loss, and cytoplasmic and axonal accumulations of fragmented mitochondria. While mitochondrial aggregates were labeled for mitophagy, mutant MFN2 did not inhibit Parkin-mediated degradation, but instead had a dominant negativ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Contributors : Rafael Yaari ; Aviva Katz ; Katherine Domb ; Keith D Harris ; Assaf Zemach ; Nir OhadSeries Type : Methylation profiling by high throughput sequencingOrganism : Physcomitrella patensDNA methylation, the addition of a methyl group to a cytosine base, is catalyzed by DNA methyltransferases (DNMTs). DNMTs evolved to mediate methylation at different contexts, genetic elements, and chromatin configurations. Plants encode for four types of DNMTs, namely methyltransferase 1 (MET1), DNA methyltransferase 3 (DNMT3), chromomethylase (CMT), and domain rearranged methyltransferase (DRM). So far, most studies focused on ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Physcomitrella patens Source Type: research
Abstract According to recent findings, the human 2-oxoglutarate dehydrogenase complex (hOGDHc) could be an important source of the reactive oxygen species in the mitochondria and could contribute to mitochondrial abnormalities associated with multiple neurodegenerative diseases, including Alzheimer's disease, Huntington disease, and Parkinson's disease. The human 2-oxoadipate dehydrogenase (hE1a) is a novel protein, which is encoded by the DHTKD1 gene. Both missence and nonsense mutations were identified in the DHTKD1 that lead to alpha-aminoadipic and alpha-oxoadipic aciduria, a metabolic disorder with a wide var...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
Abstract Cellular protein quality control (PQC) plays a significant role in the maintenance of cellular homeostasis. Failure of PQC mechanism may lead to various neurodegenerative diseases due to accumulation of aberrant proteins. To avoid such fatal neuronal conditions PQC employs autophagy and ubiquitin proteasome system (UPS) to degrade misfolded proteins. Few quality control (QC) E3 ubiquitin ligases interplay an important role to specifically recognize misfolded proteins for their intracellular degradation. Leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1) is a really interesting new gene (RIN...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
Publication date: Available online 20 February 2019Source: Stem Cell ResearchAuthor(s): Jiake Xu, Yong Fu, Weichun Xia, Jing He, Yan Zou, Wencong Ruan, Qi Lou, Ying Li, Jianwei Pan, Haifeng Li, Wei ChenAbstractThe human induced pluripotent stem cell (iPSC) line ZJUCHi002-A was established from renal epithelial cells present in urine (urinary cells) collected from an 8-year-old Charcot-Marie-Tooth disease type 2A (CMT2A) patient carrying point mutation in MFN2 (c.752C > T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. The pluripotency, capacity of...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Neurofilaments are components of the neuronal cytoskeleton and are composed of three subunits: the neurofilament heavy chain (NFEH), the medium chain (NEFM), and the light chain (NEFL). They are crucial for the growth of axons, the maintenance of axon caliber and the transmission of electrical impulses along axons.[1] Abnormal accumulation of neurofilament occurs in pathological conditions such as neurofilament inclusion disease (NFID), giant axonal neuropathy (GAN), diabetic neuropathy, spinal muscular atrophy (SMA), spastic paraplegia, Alzheimer's disease (AD) and Parkinson's disease (PD).
Source: Neuromuscular Disorders - Category: Neurology Authors: Tags: Case report Source Type: research
Publication date: Available online 14 February 2019Source: Stem Cell ResearchAuthor(s): Jiake Xu, Yanpeng Wang, Jing He, Weichun Xia, Yan Zou, Wencong Ruan, Qi Lou, Ying Li, Haifeng Li, Wei ChenAbstractThe human iPSC cell line ZJUCHi001-A was established from renal epithelial cells present in urine (urinary cells) harvested from a 2-year-old Charcot-Marie-Tooth disease type 1B (CMT1B) patient carrying point mutation in MPZ (c.292C>T). Urinary cells were reprogrammed by retrovirus vectors containing reprogramming factors: OCT4, SOX2, KLF4 and c-MYC. The pluripotency, capacity of differentiation into 3 germ layers, silenc...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Mutations in the MFN2 gene encoding Mitofusin 2 lead to the development of Charcot–Marie–Tooth type 2A (CMT2A), a dominant axonal form of peripheral neuropathy. Mitofusin 2 is localized at both the outer membrane of mitochondria and the endoplasmic reticulum and is particularly enriched at specialized contact regions known as mitochondria-associated...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
AbstractMutations inRAB18, a member of small G protein, cause Warburg micro syndrome (WARBM), whose clinical features include vision impairment, postnatal microcephaly, and lower limb spasticity. Previously, ourRab18−/− mice exhibited hind limb weakness and spasticity as well as signs of axonal degeneration in the spinal cord and lumbar spinal nerves. However, the cellular and molecular function of RAB18 and its roles in the pathogenesis of WARBM are still not fully understood. Using immunofluorescence staining and expression of Rab18 and organelle markers, we find that Rab18 associates with lysosomes and activ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
More News: Baclofen | Brain | Charcot-Marie-Tooth Disease | Health | Neurology | Neurosurgery | Study