Bauer PO, Nukina N.The pathogenic mechanisms of polyglutamine diseases and current therapeutic strategies.J Neurochem. 2009 Sep;110(6):1737-65.

Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama,
Japan.

ABSTRACT: Expansion of CAG trinucleotide repeat within the coding region of several genes
results in the production of proteins with expanded polyglutamine (PolyQ)
stretch. The expression of these pathogenic proteins leads to PolyQ diseases,
such as Huntington's disease or several types of spinocerebellar ataxias. This
family of neurodegenerative disorders is characterized by constant progression of
the symptoms and molecularly, by the accumulation of mutant proteins inside
neurons causing their dysfunction and eventually death. So far, no effective
therapy actually preventing the physical and/or mental decline has been
developed. Experimental therapeutic strategies either target the levels or
processing of mutant proteins in an attempt to prevent cellular deterioration, or
they are aimed at the downstream pathologic effects to reverse or ameliorate the
caused damages. Certain pathomechanistic aspects of PolyQ disorders are discussed
here. Relevance of disease models and recent knowledge of therapeutic
possibilities is reviewed and updated.

In last decade, a great progress has been achieved in
understanding the pathomechanism of polyQ diseases, but,
unfortunately, the therapy development does not keep up.
The challenge for the next decade will be the translation of
promising therapeutic strategies from preclinical trials to
clinical use.