Alzheimer disease has been linked to the aberrant transcription of the ubiquitin-B (UB-B) gene, caused by a +1 frame-shift during transcription. This misreading results in the translation of the dysfunctional UB-B +1 protein with the elongated C-terminus not capable of ligation to a substrate protein. Consequently, the amyloid protein within neurons is not properly ubiquitinated and degraded by proteasomes, causing the formation of amyloid plaques in Alzheimer disease-affected brain tissue. Intriguingly, the UB-B+1 frame shift product has been found in the aging human epididymis.
In segment analysis, the reduction in 20S core subunit expression was most significant in the corpus epididymis, which is in good agreement with our immunohistochemical data showing that proteasome-rich, endocytotic clear cells are particularly abundant within this epididymal segment. Clear cells have been implicated in the removal of intraluminal debris, derived from the breakdown of rejected sperm cytoplasmic droplets. The mechanism of epididymal sperm maturation and disposal of defective spermatozoa is not completely understood and may involve defective sperm marking by the UPP as well as the coating of defective spermatozoa by a procoagulatory glycoprotein, HEP64/fgl2.