The potential role of ribosomal frameshifting in generating aberrant proteins implicated in neurodegenerative diseases

Aberrant forms of proteins ubiquitin B and β-amyloid precusor protein, UBB +1 and APP +1 , are implicated in human neurodegenerative diseases. They have their carboxyl-terminal regions derived from an alternative reading frame. Transcription slippage has been invoked to explain the production of these proteins from abnormal mRNA. However, ribosomal frameshifting on wild-type mRNA may account for the great majority of the aberrant protein. Ribosomal frameshifting may also be involved in the progression of triplet expansion diseases such as Huntington's and spinocerebellar ataxias. In a particular spinocerebellar ataxia, SCA3 , Toulouse and colleagues recently discovered −1 frameshifting in a transcript containing an expanded CAG-repeat. Antibiotics that affect mammalian ribosomes may have complex effects on frameshifting and disease progression.