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Advances in molecular diagnostics for mitochondrial diseases
No full textBackground: Mitochondrial disorders (MD) are diseases caused by impairment of the mitochondrial respiratory chain. Phenotypes are polymorphous and may range from pure myopathy to multisystemic disorders. The genetic defect can be located on mitochondrial or nuclear DNA. At present, diagnosis of MD requires a complex approach: measurement of serum lactate, electromyography, muscle histology and enzymology, and genetic analysis. Magnetic resonance spectroscopy allows the assessment of tissue metabolic alterations, thus providing useful information for the diagnosis and monitoring of MD. Molecular soluble markers of mitochondrial dysfunction, at rest and during exercise, can identify the impairment of the aerobic system in MD, but a reliable biomarker for the screening or diagnosis of MD is still needed. Objective: Molecular and genetic characterization of MD, together with other experimental approaches, contribute to add new insights to these diseases. Here, the role and advances of diagnostic techniques for MD are reviewed. Conclusion: Possible applications of the results obtained by new molecular investigative approaches could in future guide therapeutic strategies. © 2009 Informa UK Ltd. All rights reserved
Exercise-Related Oxidative Stress as Mechanism to Fight Physical Dysfunction in Neuromuscular Disorders
No full textNeuromuscular diseases (NMDs) are a group of often severely disabling disorders characterized by dysfunction in one of the main constituents of the motor unit, the cardinal anatomic-functional structure behind force and movement production. Irrespective of the different pathogenic mechanisms specifically underlying these disease conditions genetically determined or acquired, and the related molecular pathways involved in doing that, oxidative stress has often been shown to play a relevant role within the chain of events that induce or at least modulate the clinical manifestations of these disorders. Due to such a putative relevance of the imbalance of redox status occurring in contractile machinery and/or its neural drive in NMDs, physical exercise appears as one of the most important conditions able to positively interfere along an ideal axis, going from a deranged metabolic cell homeostasis in motor unit components to the reduced motor performance profile exhibited by the patient in everyday life. If so, it comes out that it would be important to identify a proper training program, suitable for load and type of exercise that is able to improve motor performance in adaptation and response to such a homeostatic imbalance. This review therefore analyzes the role of different exercise trainings on oxidative stress mechanisms, both in healthy and in NMDs, also including preclinical studies, to elucidate at which extent these can be useful to counteract muscle impairment associated to the disease, with the final aim of improving physical functions and quality of life of NMD patients
Oxidative stress biomarkers are related to disease severity in mitochondrial myopathies, and may be modified by a cysteine donor
No full textA SER326CYS POLYMORPHISM IN THE DNA REPAIR GENE HOGG1 IS NOT ASSOCIATED WITH SPORADIC AD
No full textA SER326CYS POLYMORPHISM IN THE DNA REPAIR GENE HOGG1 IS NOT ASSOCIATED WITH SPORADIC ALZHEIMER'S DISEASE
No full textAssociation of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis
No full textAmyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the
spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested
that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems.
Particularly, increased levels of 8-oxoguanine and impairments of the DNA base excision repair system have been observed in neurons of ALS
patients. There is evidence that the Ser326Cys polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is associated
with a reduced DNA repair activity. To evaluate the role of the hOGG1 Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136
patients and 129 matched controls. In the total population, we observed association between both the Cys326 allele (p = 0.02) and the combined
Ser326Cys + Cys326Cys genotype (OR = 1.65, 95% CI = 1.06–2.88) and increased risk of disease. After stratification by gender, the Cys326 allele
(p = 0.01), both the Ser326Cys genotype (OR = 2.14, 95% CI = 1.09–4.19) and the combined Ser326Cys + Cys326Cys genotype (OR = 2.15, 95%
CI = 1.16–4.01) were associated with sALS risk only in males. No significant association between the Ser326Cys polymorphism and disease
phenotype, including age and site of onset and disease progression, was observed. Present results suggest a possible involvement of the hOGG1
Ser326Cys polymorphism in sALS pathogenesis
DNMT3B promoter polymorphisms and risk of late onset Alzheimer's disease.
No full textThe vast majority of Alzheimer's disease (AD) are late-onset forms (LOAD) likely due to the contribution of genetic, environmental, and stochastic factors, superimposed on a physiologically age-related decline of neuronal functions. Increasing evidence indicates epigenetic modifications in LOAD brains, and many of the environmental factors associated with AD risk, such as heavy metals and dietary factors, are able to modify the epigenome. There is also indication that environmentally-induced early life modifications of the genome during embryogenesis and brain development could contribute to the development of the disease later in life. DNA methyltransferase 3b (DNMT3b) is an enzyme involved in de novo methylation of the epigenome during embryogenesis, expressed in progenitor cells during neurogenesis. In the present study we evaluated two functional DNMT3B promoter polymorphisms, namely -149 C>T (rs2424913) and - 579 G>T (rs1569686), as candidate LOAD risk factors. Our analysis of 376 Italian LOAD patients and 308 matched controls revealed no difference in allele frequencies between the case an the control group (OR = 1.10 (0.88-1.39) for rs2424913, and OR = 1.02 (0.81-1.28) for rs1569686). Also the genotype distributions of both polymorphisms were closely similar between groups, and no significant effect on disease age at onset was observed. Overall, present results do not support a major role for rs2424913 or rs1569686 in LOAD pathogenesis
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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