Adv Exp Med Biol
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Fragile X syndrome (FXS), a severe neurodevelopmental anomaly, and one of the earliest disorders linked to an unstable ('dynamic') mutation, is caused by the large (>200) CGG repeat expansions in the noncoding portion of the FMR1 (Fragile X Mental Retardation-1) gene. These expansions, termed full mutations, normally silence this gene's promoter through methylation, leading to a gross deficit of the Fragile X Mental Retardation Protein (FMRP) that is essential for normal brain development. Rare individuals with the expansion but with an unmethylated promoter (and thus, FMRP production), present a much less severe form of FXS. ⋯ Special emphasis has been placed on the possibility that the modest elevation of 'toxic' FMR1 mRNA in the carriers of grey zone alleles may present an additional risk for some neurodegenerative diseases, such as those associated with parkinsonism, by synergizing with either other susceptibility genes or environmental poisons. The present status ofthe treatment of fragile X-related disorders, especially FXS, is presented in the last section of this chapter. Pharmacological interventions in this syndrome have recently extended beyond stimulants and antipsychotic medications, and the latest trials involving a group of GluR5 antagonists aim to ascertain if these substances have the potential to reverse some of the neurobiological abnormalities of FXS.
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Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. Among the new treatments currently being investigated, immunotherapy is theoretically very attractive since it offers the potential for high tumor-specific cytotoxicity. Increasing numbers of reports demonstrate that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. ⋯ Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response in patients with glioma, where it seems to be safe and without major side effects. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy. Its efficacy should be further determined in randomized, controlled clinical trials.
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The spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterised by progressive lack of motor coordination leading to major disability. SCAs show high clinical, genetic, molecular and epidemiological variability. ⋯ The scope of this chapter is to provide an updated information on Machado-Joseph disease (MJD), the most frequent SCA subtype worldwide and other rare spinocerebellar ataxias including dentatorubral-pallidoluysian atrophy (DRPLA), the X-linked fragile X tremor and ataxia syndrome (FXTAS) and the nonprogressive episodic forms of inherited ataxias (EAs). Furthermore, the different therapeutic strategies that are currently being investigated to treat the ataxia and non-ataxia symptoms in SCAs are also described.
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Tourette syndrome (TS) is a neurodevelopmental disorder consisting of multiple motor and one or more vocal/phonic tics. TS is increasingly recognized as a common neuropsychiatric disorder usually diagnosed in early childhood and comorbid neuropsychiatric disorders occur in approximately 90% of patients, with attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) being the most common ones. Moreover, a high prevalence of depression and personality disorders has been reported. ⋯ The current diagnostic systems have dictated that TS is a unitary condition. However, recent studies have demonstrated that there may be more than one TS phenotype. In conclusion, it appears that TS probably should no longer be considered merely a motor disorder and, most importantly, that TS is no longer a unitary condition, as it was previously thought.