p53-mediated disruption of FIP200 function cause autophagic dysregulation in a SCA7 polyglutamine disease model

Excerpt

Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine domains [1]. Aggregation of the different polyglutamine (polyQ) expanded disease proteins have been linked to the toxicity in these disorders [1]. We and others have shown that polyQ expanded proteins can be degraded by autophagy [2], and pharmacological activation of this pathway has hence been suggested as a therapeutic approach for these disorders. However, lately increasing evidence indicating that autophagy dysfunction occurs in several neurodegenerative disorders has emerged and raised concerns regarding using stimulation of this pathway as a therapeutic approach [3]. The aim of this study was to determine if and by which molecular mechanism(s) the expanded SCA7 disease protein ataxin-7 (ATXN7) affects the autophagic process. …