In addition to the well-known polyglutamine diseases (see FBhh0000001), there are a number of characterized polyalanine diseases in humans (see Albrecht and Mundlos, 2005; pubmed:15917204). Two of these diseases, oculopharyngeal muscular dystrophy (FBhh0000183) and panhypopituitarism, X-linked, with or without intellectual disability (FBhh0001342), have been modeled in flies. General models of polyalanine disorders in flies have been developed using synthetic constructs with polyalanine runs of various lengths; these are described in FlyBase as alleles of the synthetic gene Zzzz\Poly-Ala. Runs of short nucleotide repeats may also result in pathologies effected via the transcript(s) of a gene, rather than the protein products. Work in Drosophila addressing this phenomenon is described in a separate disease report; see RNA-repeat diseases (FBhh0000059).
[updated Apr.2021 by FlyBase; FBrf0222196]
The process of intracellular aggregation of polyalanine-containing molecules differs from that of polyglutamine-containing molecules. Polyalanine does not form amyloid under normal cellular conditions, but instead forms α-helical clusters, thus disrupting normal protein function (Polling et al., 2015; pubmed: 26571108).
