Curcumin-cyclodextrin/cellulose Nanocrystals Improve the Phenotype of Charcot-Marie-Tooth-1A Transgenic Rats Through the Reduction of Oxidative Stress.

Curcumin-cyclodextrin/cellulose Nanocrystals Improve the Phenotype of Charcot-Marie-Tooth-1A Transgenic Rats Through the Reduction of Oxidative Stress. Free Radic Biol Med. 2020 Sep 24;: Authors: Caillaud M, Msheik Z, Ndong-Ntoutoume GM, Vignaud L, Richard L, Favreau F, Faye PA, Sturtz F, Granet R, Vallat JM, Sol V, Desmoulière A, Billet F Abstract The most prevalent form of Charcot-Marie-Tooth disease (CMT type 1A) is characterized by duplication of the PMP22 gene, peripheral dysmyelination and decreased nerve conduction velocities leading to muscle weakness. Recently, oxidative stress was reported as a feature in CMT1A patients. Curcumin exhibits antioxidant activities and has shown beneficial properties on peripheral nerves. However, curcumin presents unfavorable pharmacokinetics. We developed curcumin-cyclodextrin/cellulose nanocrystals (Nano-Cur) to bypass this limitation. The present study investigated the therapeutic potential of Nano-Cur in vitro in Schwann cells (SCs) and in vivo in the transgenic CMT1A rat model. In vitro, Nano-Cur treatment (0.01 μM for 8h) reduced reactive oxygen species and improved mitochondrial membrane potential in CMT1A SCs. Moreover, Nano-Cur treatment (0.01 μM for 1 week) increased the expression of myelin basic protein in SCs/neurons co-cultures. Primary in vivo experiments carried out in WT rats showed that intraperitoneal (i.p.) injection of Nano-Cur treatment containing 0.2 mg/kg of curcumin strongly e...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research

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ConclusionThe finding of aHADHA mutation as a cause of CMT is of interest because its encoded protein is a subunit of the mitochondrial trifunctional protein (MTP) complex, a mitochondrial enzyme involved in long chain fatty acid oxidation. Long chain fatty acid oxidation is an important source of energy for skeletal muscles. The mutation found in CMT2-102 is only the second intronic mutation reported inGDAP1. The mutation in the CMT2-102 pedigree was outside the canonical splice site sequences, emphasizing the importance of careful examination of available intronic sequences in exome sequence data.
Source: Journal of Neurology - Category: Neurology Source Type: research
A causal relationship between Mitofusin (MFN) 2 gene mutations and the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2A (CMT2A) was described over 15 years ago. During the intervening period much has been learned about MFN2 functioning in mitochondrial fusion, calcium signaling, and quality control, and the consequences of these MFN2 activities on cell metabolism, fitness, and development. Nevertheless, the challenge of defining the central underlying mechanism(s) linking mitochondrial abnormalities to progressive dying-back of peripheral arm and leg nerves in CMT2A is largely unmet. Here, a different persp...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Authors: Khosravi S, Harner ME Abstract Mitochondria perform a plethora of functions in various cells of different tissues. Their architecture differs remarkably, for instance in neurons versus steroidogenic cells. Furthermore, aberrant mitochondrial architecture results in mitochondrial dysfunction. This indicates strongly that mitochondrial architecture and function are intimately linked. Therefore, a deep knowledge about the determinants of mitochondrial architecture and their function on a molecular level is of utmost importance. In the past decades, various proteins and protein complexes essential for formatio...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
This study will also allow us to better comprehend the problem of proteinopathies linked with aberrant protein accumulation and open new possibilities to better elucidate the molecular mechanisms involved in the pathologies of neurodegeneration and aging. PMID: 31982566 [PubMed - as supplied by publisher]
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
Authors: Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR Abstract Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
In conclusion, our work supports that the molecular diagnostic rate of CMT2 patients can be increased via whole exome sequencing, and our data suggest that assessment of possibleHINT1 mutations should be undertaken for CMT2 patients with neuromyotonia.
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research
Authors: Murakami T, Sunada Y Abstract Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy and genetically heterogeneous. CMT1 and CMTX are autosomal dominant and X-linked demyelinating neuropathies, respectively. CMT1A, CMT1B, and CMTX1 are the common forms of CMT, which are attributed to the genes encoding the myelin or gap junction proteins expressed in the myelinating Schwann cells. CMT4 is a rare autosomal recessive demyelinating neuropathy that usually shows an early-onset severe phenotype. Twelve genes have been described as CMT4, which encodes many kinds of proteins including mitochon...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Apoptosis-Inducing Factor Mitochondria-associated-1 gene (AIFM1) encodes a mitochondrial flavin adenine dinucleotide-dependent nicotinamide oxidoreductase, which has a biological role in oxidative phosphorylation (OXPHOS) and in apoptosis pathway [1]. AIFM1 mutations have been reported to be associated with various neurological diseases, including Cowchock syndrome (OMIM 310490) [2], X-linked recessive Charcot-Marie-Tooth disease-4 (CMTX4), X-linked deafness-5 (DFNX5; OMIM 300614) [3], and hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) [4].
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
Abstract Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson's disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders. However, whether and how mitochondrial impairment activat...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Abstract Charcot-Marie-Tooth (CMT) disease is a common inherited peripheral neuropathy. The CMT2K axonal form is associated with GDAP1 dominant mutations, which according to the affected domain cause a gradient of severity. Indeed, the p.C240Y mutation, located within GDAP1 glutathione S-transferase (GST) domain and associated to a mitochondrial complex I defect, is related to a faster disease progression, compared to other mutations, such as the p.R120W located outside the GST domain. Here, we analysed the pathophysiology of six CMT2K fibroblast cell lines, carrying either the p.C240Y or p.R120W mutations. We sho...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
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