[Show abstract][Hide abstract] ABSTRACT: There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease, is caused by gene-environment interactions. In fact, given that only about 10% of all ALS diagnosis has a genetic basis, gene-environmental interaction may give account for the remaining percentage of cases. However, relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron degeneration leading to ALS, although exposure to chemicals-including lead and pesticides-agricultural environments, smoking, intense physical activity, trauma and electromagnetic fields have been associated with an increased risk of ALS. This review provides an overview of our current knowledge of potential toxic etiologies of ALS with emphasis on the role of cyanobacteria, heavy metals and pesticides as potential risk factors for developing ALS. We will summarize the most recent evidence from epidemiological studies and experimental findings from animal and cellular models, revealing that potential causal links between environmental toxicants and ALS pathogenesis have not been fully ascertained, thus justifying the need for further research.
International Journal of Molecular Sciences 08/2013; 14(8):15286-311. DOI:10.3390/ijms140815286 · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: β-N-methylamino-l-alanine (L-BMAA) is a neurotoxic amino acid that has been related to various neurodegenerative diseases. The aim of this work was to analyze the biotoxicity produced by L-BMAA in vivo in rats, trying to elucidate its physiopathological mechanisms and to search for analogies between the found effects and pathologies like Amyotrophic Lateral Sclerosis (ALS). Our data demonstrated that the neurotoxic effects in vivo were dosage-dependent. For evaluating the state of the animals, a neurological evaluation scale was developed as well as a set of functional tests. Ultrastructural cell analysis of spinal motoneurons has revealed alterations both in endoplasmic reticulum and mitochondria. Since GSK3β could play a role in some neuropathological processes, we analyzed the alterations occurring in GSK3β levels in L-BMAA treated rats, we have observed an increase in the active form of GSK3β levels in lumbar spinal cord and motor cerebral cortex. On the other hand, (TAR)-DNA-binding protein 43 (TDP-43) increased in L-BMAA treated animals. Our results indicated that N-acetylaspartate (NAA) declined in animals treated with L-BMAA, and the ratio of N-acetylaspartate/choline (NAA/Cho), N-acetylaspartate/creatine (NAA/Cr) and N-acetylaspartate/choline+creatine (NAA/Cho+Cr) tended to decrease in lumbar spinal cord and motor cortex. This project offers some encouraging results that could help establishing the progress in the development of an animal model of sporadic ALS and L-BMAA could be a useful tool for this purpose.
[Show abstract][Hide abstract] ABSTRACT: in animal models such as SOD1 transgenic mice, cell based models, autopsy studies and molecular genetic Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. The current status of the epidemiology,
challenges to its study, and novel study design options are discussed in this paper. We focus on recent results from
large-scale population based prospective studies, case-control studies and population based registries, risk factors, and
neuropathologic fi ndings in chronic traumatic encephalomyelopathy. We identify areas of interest for future research,
including time-trends in the incidence and prevalence of ALS; the meaning of lifetime risk; the phenotypic description of
ALS; the defi nition of familial versus sporadic ALS, syndromic aspects of ALS; specifi c risk factors such as military
service, life style factors such as smoking, the use of statins, and the presence of β -N-methylamino-L-alanine (BMAA),
an excitotoxic amino acid derivative possibly produced by cyanobacteria found in almost every terrestrial and aquatic
habitat; the emergence and disappearance of an endemic ALS in areas of the Pacifi c; and gene-environment interactions
in the etiology of ALS. To move the epidemiology forward, we suggest using well-characterized cohorts of newly diagnosed
ALS patients to identify risk and prognostic factors; storing biological material for future studies; building on the National
ALS Registry as a resource of future studies; working in multidisciplinary consortia; and addressing the possible early life
etiology of ALS.
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