Alterations in presenilin 1 processing by amyloid-beta peptide in the rat retina.
Accumulating evidence indicates that mutations in the presenilin 1 (PS1) gene are responsible for most cases of familial Alzheimer's disease (AD). Although its biological functions are not yet fully understood, it appears that PS1 plays a role in the processing and trafficking of the amyloid precursor protein (APP). However, little is known about factors that are involved in regulating the metabolism of PS1 especially in relation to AD pathology. In this study, we have examined the effect of optic nerve crush, intravitreal injection of the inflammatory agent lipopolysaccharide (LPS) or injection of amyloid beta(1-42) (A beta(1-42)) on the expression and processing of PS1 in the rat retina. We found that 48 h after injection of A beta(1-42) there was a dramatic alteration in the banding pattern of PS1 on Western blots, as indicated by marked changes in the levels of expression of some of its C- and N-terminal fragments in retinal homogenates. These results suggest an A beta(1-42)-induced potentiation of a non-specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model.
Watts
Helena R
HR
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Campus, Fulham Palace Road, London, W6 8RF, UK.
Vince
Valerie
V
Walsh
Desmond T
DT
Bresciani
Laura G
LG
Gentleman
Stephen M
SM
Jen
Ling-Sun
LS
Anderson
Peter J B
PJ
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020221:Optic Nerve Injuries / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D053764:Presenilin-1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42)