Redox proteomics identification of oxidatively modified brain proteins in inherited Alzheimer's disease: an initial assessment.
OBJECTIVE
To identify oxidatively modified proteins in brains of persons with inherited Alzheimer's disease.


METHODS
Redox proteomics was used to identify oxidatively modified brain proteins in persons with mutations in the genes for presenilin-1 (PS-1).


RESULTS
An initial redox proteomics assessment of oxidatively modified proteins from brains of individuals with PS-1 mutations was performed. These PS1 mutations, Q222H and M233T, are completely penetrant causing early-onset familial AD as previously reported in these Australian families. We show that oxidative modifications of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), gamma-enolase, actin, and dimethylarginine dimethylaminohydrolase 1 (DMDMAH-1) are present in the brain of familial AD subjects.


CONCLUSIONS
These initial results suggest that oxidatively modified proteins are important common features in both familial and sporadic AD.
Butterfield
D Allan
DA
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA. dabcns@uky.edu
Gnjec
Anastazija
A
Poon
H Fai
HF
Castegna
Alessandra
A
Pierce
William M
WM
Klein
Jon B
JB
Martins
Ralph N
RN
D000199:Actins / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000581:Amidohydrolases / Q000235:genetics; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology; D010751:Phosphopyruvate Hydratase; D053764:Presenilin-1 / Q000235:genetics*; D040901:Proteomics; D043222:Ubiquitin Thiolesterase / Q000235:genetics
D000199:Actins; D053764:Presenilin-1; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase; D000581:Amidohydrolases; C059999:dimethylargininase; D010751:Phosphopyruvate Hydratase