Neuropeptide research discloses part of the secrets of Alzheimer's disease neuropathogenesis: state of the art 2004.
Molecular misreading, a process discovered in the late 1990s, entails the formation of aberrant transcripts due to the inaccurate conversion of genomic information, and results in an accumulation of aberrant proteins. The aberrant transcripts are formed as a result of a dinucleotide deletion (e.g. DeltaGA, DeltaGU) during or after transcription. Either the RNA polymerase starts to make mistakes (e.g. stuttering) in simple sequence repeats, such as GAGAG, or erroneous editing of transcripts occurs. If these aberrant transcripts are not detected and degraded efficiently, they can be translated from the deletion onwards into the +1 reading frame. The resulting proteins are therefore called +1 proteins. If functional domains are located downstream of the frameshift site, the result will be a protein with a potential loss or gain of function. It has been hypothesized that quality control mechanisms for both transcripts and proteins work less efficiently during aging, which is why +1 proteins may become manifest and contribute to age-related diseases in neuronal and non-neuronal cells.
van Leeuwen
F W
FW
Research Team Molecular Misreading, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The Netherlands. f.van.leeuwen@nih.knaw.nl
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics; D006801:Humans; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D025801:Ubiquitin / Q000172:deficiency / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D009097:Multienzyme Complexes; D009479:Neuropeptides; D011506:Proteins; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex