Chapter

Molecular mechanisms in juvenile Huntington’s disease

Roman Gonitel and Ferdinando Squitieri

in Juvenile Huntington's Disease

Published on behalf of Oxford University Press

Published in print January 2009 | ISBN: 9780199236121
Published online November 2012 | e-ISBN: 9780191753213 | DOI: http://dx.doi.org/10.1093/med/9780199236121.003.0006
Molecular mechanisms in juvenile Huntington’s disease

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There are both common and specific pathogenic mechanisms in the HD spectrum. Upstream factors like CAG repeat length and processes like polyglutamine-mediated protein misfolding would be common to all cases of HD. However, more downstream events in the disease cascade would differ between HD clusters, especially JHD, as is discussed in this chapter. Therapeutic targeting of the common pathogenic mechanisms would be applicable to all HD patients. From this perspective, unravelling the mechanisms influencing expansion transmission and CAG instability represent a crucial issue to be solved for future therapeutic strategies. On the other hand, understanding the mechanisms that produce variability in the presentation and progression of HD symptoms is relevant both clinically and therapeutically. This would allow us to determine whether there are specific treatments that should benefit a limited cohort of HD patents. Cell and animal models of HD will continue to be critical in unravelling pathological mechanisms of the disease. The associated analysis of patients and families, together with the study of human tissues, will complement and validate these approaches. Some particular human phenotypes such as infantile forms or homozygotes, associated with an amplification of polyglutamine toxicity, may represent in vivo study models themselves. Once a potential difference of HD pathogenic mechanisms has been demonstrated in patients, selected according to their clinical and genetic features, a fine analysis of the biological aspects of their tissues (DNA and cell lines) will offer additional clues to the underlying cell pathology which in turn can be extended to other patients.

Chapter.  7044 words. 

Subjects: Neurology

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