Misframed Proteins and Neurodegeneration: A Novel View on Alzheimer’s and Parkinson’s DiseasesDennissen F.J.A. · Kholod N. · Steinbusch H.W.M. · Van Leeuwen F.W.
DepartmentofNeuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
Sporadic forms of Alzheimer’s and Parkinson’s diseases are the most frequent forms of their kind. Together with Huntington’s disease, they belong to the so called ‘conformational diseases’ as they share a common feature in the accumulation of insoluble protein deposits. In this review, we focus on the significance of the ubiquitin-proteasome system in conformational diseases and the possible consequences due to the accumulation of aberrant proteins. In all forms of Alzheimer’s and Huntington’s diseases, but not in Parkinson’s disease, we have shown the presence of misframed proteins such as misframed ubiquitin (UBB+1) of which we have determined the functional relevance in vitro and in vivo.Misframed proteins are the result of the inaccurate transcription of monotonic sequences in the genome and their subsequent translation. This process has been called ‘molecular misreading’. In the present review, we will discuss the present state of the art with regard to UBB+1 and amyloid precursor protein APP+1.
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