About this Research Topic
Spinocerebellar ataxias (SCAs) are a group of inherited neurodegenerative disorders and rare diseases with a prevalence of 1-5:100,000 individuals in autosomal-dominant cerebellar ataxias (ADCAs) and are characterized by ocular motor abnormalities, cognitive dysfunction, peripheral neuropathy, and progressive cerebellar ataxia. Most SCAs share clinical features ranging from pure cerebellar manifestations to mixed cerebellar and brain stem disorders.
The major causes of genetically inherited SCAs are suggested by expansions of simple nucleotide repeats in specific genes. The SCA1, SCA2, SCA3 (also known as Machado-Joseph disease), SCA6, SCA7, and SCA17 are caused by the expansion of CAG repeats encoding glutamine in coding regions or polyglutamine (polyQ) domain in disease proteins. Unlike polyQ SCAs, Repeat-associated non-ATG translation (RAN translation), which is founded in microsatellite disorders and can produce unexpected homopolymeric proteins in various reading frames in non-AUG start codon, is believed to be found in several types of SCA including SCA8, 10, 31, 36, and C9orf72-linked ALS as well. The non-repeat mutations may also contribute to the development of several SCAs including SCA5, SCA9, SCA13, SCA10, SCA14, and SCA27.
Although there are several molecular mechanisms underlying SCA pathogenesis, such as protein aggregation, proteasomal stress, intranucleus inclusion body formation, RNA-toxicity, and autophagy pathway, most SCAs showed that neurodegeneration occurs in the cerebellum and brain stem areas and therefore causes a loss of Purkinje cells, decreased cell numbers in molecular and granular layers, and loss of cells in the pontine nucleli.
This Research Topic seeks contributions focusing on molecular, cellular, and physiological mechanisms of neurodegeneration in the SCA. We also encourage scientists who discover potential therapeutic targets, therapeutic molecules including small molecules and biologic drugs to submit their manuscripts. We welcome a variety of article types: original research, review, hypothesis and theory.
The understanding of pathophysiology and molecular mechanisms of SCAs requires multidisciplinary approaches ranging from molecular, cellular biology, proteomic and transcriptomic analysis, cerebellar physiology, medicinal chemistry, transgenic model animal study, and clinical approaches. Such understanding would contribute to the development of effective treatment of SCAs.
Keywords: spinocerebellar ataxia (SCA), poly-glutamine repeats, cerebellar physiology, neurodegenerative disease, Repeat-associated non-ATG translation (RAN translation)
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