Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease.
Seladin-1 is a gene recently shown to be down-regulated in brain regions selectively degenerated in Alzheimer's disease. The sequence of seladin-1 shares similarities with flavin-adenine-dinucleotide-dependent oxidoreductases and it has been found to protect cells from apoptotic cell death. In this work, we show that the transcription of seladin-1 is selectively down-regulated in the brain areas affected in Alzheimer's disease. The down-regulation in seladin-1 transcription was associated with hyperphosphorylated tau seen as linkage to immunohistochemically detected paired helical filament tau, neuritic plaques and neurofibrillary tangles. In contrast, no association was found between seladin-1 transcription and beta-amyloid deposition when analyzing human samples or tissue from transgenic animals. Furthermore, the relative transcription of seladin-1 was found to fluctuate during aging in the transgenic mouse model of Alzheimer's disease. The fluctuation was enhanced by Alzheimer's disease causing mutations in presenilin-1 and amyloid precursor protein genes. Finally, seladin-1 transcription was found to be up-regulated in mouse N2a cells induced to undergo apoptosis with okadaic acid. The results presented here indicate that seladin-1 transcription is selectively down-regulated in brain regions vulnerable to Alzheimer's disease and this down-regulation is associated with the hyperphosphorylation of tau protein.
Iivonen
S
S
Department of Neuroscience and Neurology, University Hospital and University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland. susan.iivonen@uku.fi
Hiltunen
M
M
Alafuzoff
I
I
Mannermaa
A
A
Kerokoski
P
P
Puoliväli
J
J
Salminen
A
A
Helisalmi
S
S
Soininen
H
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D002102:Cadaver; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D009419:Nerve Tissue Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; C437069:3beta-hydroxysterol delta24-reductase; C499055:DHCR24 protein, human; C499056:Dhcr24 protein, mouse