Journal of the neurological sciences
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The mitochondria have several important functions in the cell. A mitochondrial dysfunction causes an abatement in ATP production, oxidative damage and the induction of apoptosis, all of which are involved in the pathogenesis of numerous disorders. This review focuses on mitochondrial dysfunctions and discusses their consequences and potential roles in the pathomechanism of neurodegenerative disorders. ⋯ In certain disorders, there is a quinolinic acid overproduction, while in others the alterations in brain kynurenic acid levels are more pronounced. A more precise knowledge of these alterations yields a basis for getting better therapeutic possibilities. The last part of the review discusses metabolic disturbances and changes in the kynurenine metabolic pathway in Parkinson's, Alzheimer's and Huntington's diseases.
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Genetic predisposition to stroke has been proven in animal models and in humans. Unraveling the genetic factors that play a role in common stroke is very difficult, as the causation of stroke is multifactorial (a combination of environmental and genetic risk factors) and the genetic part is very complex (polygenic, multiple genes play a role). Many common risk factors for stroke like diabetes and arterial hypertension are partly inherited, so many genetic loci contribute more or less to the stroke phenotype. ⋯ These disorders can serve as models to study environmental or genetic factors that contribute also to the common forms of stroke. Animal model of stroke can also provide valuable information on genetic factors involved in stroke predisposition. In this review, the focus lies on monogenic forms of stroke that can serve as models to study the more common phenotypes.
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Relapses in multiple sclerosis (MS) have wide-ranging consequences for patients and should be actively controlled with an appropriate immunomodulating agent provided soon after the diagnosis of MS. Several agents with varying mechanisms of action are approved for use in treating MS. Here we take a brief look at several short- and long-term comparative trials, examining the established strengths and weaknesses of the available immunomodulators. By reviewing the existing comparisons, clinicians will better understand the factors determining when to initiate therapy with an immunomodulator and how to determine which of these treatments may best suit their patients' needs.
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Botulinum toxin type A (BTX-A) is best known to neurologists as a treatment for neuromuscular conditions such as dystonias and spasticity and has recently been publicized for the management of facial wrinkles. The property that makes botulinum toxin type A useful for these various conditions is the inhibition of acetylcholine release at the neuromuscular junction. ⋯ This observation led to trials of botulinum neurotoxins in various conditions involving autonomic innervation. The article reviews the emerging use of botulinum neurotoxins in these and selected other conditions, including sialorrhea, primary focal hyperhidrosis, pathological pain and primary headache disorders that may be of interest to neurologists and related specialists.
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Review
Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia.
There is significant evidence that the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia (FRDA), multiple sclerosis and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) associated with mitochondrial dysfunction. The mitochondrial genome may play an essential role in the pathogenesis of these diseases, and evidence for mitochondria being a site of damage in neurodegenerative disorders is based in part on observed decreases in the respiratory chain complex activities in Parkinson's, Alzheimer's, and Huntington's disease. Such defects in respiratory complex activities, possibly associated with oxidant/antioxidant imbalance, are thought to underlie defects in energy metabolism and induce cellular degeneration. ⋯ Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. This may open up new perspectives in medicine, as molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. In particular, manipulation of endogenous cellular defense mechanisms, such as the heat shock response, through nutritional antioxidants, pharmacological compounds or gene transduction, may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration.