Lancet neurology
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Alzheimer's disease and other idiopathic dementias are associated with epigenetic transformations. These transformations connect the environment and genes to pathogenesis, and have led to the investigation of epigenetic-based therapeutic targes for the treatment of these diseases. Epigenetic changes occur over time in response to environmental effects. ⋯ We posit that the LEWAS design could lead to effective prevention and treatments by identifying potential therapeutic strategies. Epigenetic evidence suggests that dementia is not a suddenly occurring and sharply delineated state, but rather a gradual change in crucial cellular pathways, that transforms an otherwise healthy state, as a result of neurodegeneration, to a dysfunctional state. Evidence from epigenetics could lead to ways to detect, prevent, and reverse such processes before clinical dementia.
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Movement disorders in children are causally and clinically heterogeneous and present in a challenging developmental context. Treatment options are broad ranging, from pharmacotherapy to invasive neuromodulation and experimental gene and stem cell therapies. ⋯ Identification of the most appropriate treatment is uniquely challenging in children because of the incomplete knowledge about the pathophysiology of movement disorders and their influence on normal motor development; thus, effective therapeutic options for these children remain an unmet need. It is vital to transfer the expanding knowledge of the movement disorders into the development of novel symptomatic or, ideally, disease-modifying treatments, and to assess these therapeutic strategies in appropriately designed and well done trials.
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Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. ⋯ NIH, NINDS, NHMRC, CIHR, European national research institutions, Fondation Leducq.
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Protein aggregates are hallmarks of nearly all age-related neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and several polyglutamine diseases such as Huntington's disease and different forms of spinocerebellar ataxias (SCA; SCA1-3, SCA6, and SCA7). The collapse of cellular protein homoeostasis can be both a cause and a consequence of this protein aggregation. ⋯ Heat shock proteins (HSPs) play a central part in regulating protein quality control and contribute to protein aggregation and disaggregation. Therefore, HSPs are viable targets for the development of drugs aimed at reducing pathogenic protein aggregates that are thought to contribute to the development of so many neurodegenerative disorders.