Abstract
Decades of research into the structure and function of the cerebellum have led to a clear understanding of many of its cells and their sub-cellular level, but the cerebellum remains a mystery. It has more neurons than the rest of the CNS suggesting that its function is important and complicated.
Positron emission tomography (PET) as well as functional magnetic resonance imaging (fMRI) was used to study changes in cerebellar activations as an effect of learning. New findings suggest that the cerebellum plays a role in multiple functional domains: motor as well as cognitive, affective, and sensory.
A number of functional hypotheses have recently been advanced to account for how the cerebellum may contribute to cognition. The resource to use molecular techniques to establish the genetic diagnoses of the autosomal dominant ataxias has revolutionized the field.
Presently, it is possible to systematically classify these disorders according to the nature of the causative mutation, with implications for dia-gnostic testing, and analysis of pathogenesis strategies. Ataxias caused by CAG repeat expansions that encode polyglutamine, ataxias caused by mutations in ion channels, ataxias caused by repeat expansions that do not encode polyglutamine, and ataxias caused by point mutations are distinguished.
Recent evidence has shown that transcriptional dysregulation is a relevant event in the pathogenesis of polyglutamine-induced neurodegeneration in SCAs and an early target of polyglutamine toxicity. No specific treatments exist for most types of hereditary ataxia.
New technologies such as microarray expressions, proteome analyses, as well as PET, fMRI hold up hopes for not only the identification of affected pathways but also consequently effective therapy.