687 research outputs found
Amyloid-β in mitochondrial disease: mutation in a human metallopeptidase links amyloidotic neurodegeneration with mitochondrial processing.
There is increasing evidence that common molecular pathways in neurons are closely linked with mitochondrial function and that mitochondrial dysfunction is connected to various forms of neurodegenerative diseases. For instance, mitochondria are involved in amyloid‐β (Aβ) deposition in Alzheimer's disease, although the exact molecular pathways remain largely unknown. Brunetti et al (2015) in this issue of EMBO Molecular Medicine provide a novel link between Aβ accumulation and mitochondria. A pathogenic mutation in a Norwegian family in the mitochondrial metallopeptidase PITRM1 is found to underlie a novel mitochondrial neurodegenerative phenotype associated with Aβ accumulation
Modifying Mitochondrial tRNAs: Delivering What the Cell Needs
Protein synthesis is critically dependent on transfer (t)-RNAs, but the factors regulating tRNA function are poorly understood. In this issue of Cell Metabolism, Wei et al. (2015) show that Cdk5 regulatory subunit-associated protein-like-1 synchronizes mitochondrial and cytosolic translation in response to external stress, providing key insight into the pathogenesis of a common inherited mitochondrial disease
A practical review on the measurement tools for cellular adhesion force
Cell cell and cell matrix adhesions are fundamental in all multicellular
organisms. They play a key role in cellular growth, differentiation, pattern
formation and migration. Cell-cell adhesion is substantial in the immune
response, pathogen host interactions, and tumor development. The success of
tissue engineering and stem cell implantations strongly depends on the fine
control of live cell adhesion on the surface of natural or biomimetic
scaffolds. Therefore, the quantitative and precise measurement of the adhesion
strength of living cells is critical, not only in basic research but in modern
technologies, too. Several techniques have been developed or are under
development to quantify cell adhesion. All of them have their pros and cons,
which has to be carefully considered before the experiments and interpretation
of the recorded data. Current review provides a guide to choose the appropriate
technique to answer a specific biological question or to complete a biomedical
test by measuring cell adhesion
Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases.
Defects of RNA metabolism have been increasingly identified in various forms of inherited neurological diseases. Recently, abnormal RNA degradation due to mutations in human exosome subunit genes has been shown to cause complex childhood onset neurological presentations including spinal muscular atrophy, pontocerebellar hypoplasia and myelination deficiencies. This paper summarizes our current knowledge about the exosome in human neurological disease and provides some important insights into potential disease mechanisms
How to Cite this article: WHAT EVIDENCE IS THERE FOR BIOCHEMICAL TESTING? http://www.ifcc.org/ejifcc/vol14no3/140310200306n.htm WHAT EVIDENCE IS THERE FOR BIOCHEMICAL TESTING?
A variable neurodegenerative phenotype with polymerase gamma mutation
mtDNA replication and repair, causes mitochondrial diseases including autosomal dominant
progressive external ophthalmoplegia (PEO),1 childhood hepato-encephalopathy (Alpers–
Huttenlocher syndrome), adult-onset spinocerebellar ataxia, and sensory nerve degeneration with
dysarthria and ophthalmoparesis (SANDO)
Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'.
BACKGROUND: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking. OBJECTIVE: We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies. METHODS: We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale. RESULTS: Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH). CONCLUSIONS: The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies
Progressive Chronic Inflammatory Demyelinating Polyneuropathy in a Child with Central Nervous System Involvement and Myopathy
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic disorder, manifesting with monophasic or
relapsing course. Progressive course is rare in children. The article presents a boy with progressive generalized muscle
weakness and areflexia since the age of two, developed after viral infection. Electromyoneurography showed severe neurogenic
lesion, with myopathic pattern in proximal muscles. Increased serum ganglioside antibody titers (anti-GM1
and anti-GD1b) were registered. Sural nerve biopsy revealed demyelination and onion bulbs. Inflammatory perivascular
CD3 positive infiltrates were present in muscle and nerve biopsies. Brain magnetic resonance imaging showed cortical
atrophy, hyperintensities of the white matter and gray matter hypointensities. Improvement occurred on intravenous immune
globulins and methylprednisolone treatment. Demyelination might develop in central and peripheral nervous system
associated with inflammatory myopathy in patients with progressive course of CIDP
Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain.
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