Polyglutamine genes interact to modulate the severity and progression of neurodegeneration in Drosophila.

摘要: The expansion of polyglutamine tracts in a variety proteins causes devastating, dominantly inherited neurodegenerative diseases, including six forms spinal cerebellar ataxia (SCA). Although encoded single allele each the responsible genes is sufficient for onset disease, clinical observations suggest that interactions between these may affect disease progression. In screen modifiers neurodegeneration due to SCA3 Drosophila, we isolated atx2, fly ortholog human gene related ataxia, SCA2. We show normal activity Ataxin-2 (Atx2) critical degeneration and Atx2 hastens nuclear inclusions associated with SCA3. These activities depend on conserved protein interaction domain Atx2, PAM2 motif, which mediates binding cytoplasmic poly(A)-binding (PABP). here PABP also influences SCA3-associated neurodegeneration. studies indicate toxicity one can be dramatically modulated by another. propose functional links are severity progression, such therapeutics applicable others.