Protein levels of heat shock proteins 27, 32, 60, 70, 90 and thioredoxin-1 in amnestic mild cognitive impairment: an investigation on the role of cellular stress response in the progression of Alzheimer disease.
Heat shock proteins (HSPs) are highly regulated proteins that are involved in normal cellular activity and are up-regulated when the cell is exposed to stress such as heat or excess reactive oxygen species (ROS) production. HSPs are molecular chaperones that mediate the proper folding of proteins and promote recovery of the native conformations of proteins lost due to stress. Improperly folded or denatured proteins tend to aggregate and accumulate in cells. A number of neurodegenerative diseases such as Parkinson disease (PD) and Alzheimer disease (AD) have been called "protein misfolding disorders" due their characteristic pathology. Until now the exact mechanism(s) of AD progression and pathogenesis largely remains unknown. Reasoning that stress is present in brain in AD, we tested the suggestion that HSP levels would be increased in amnestic mild cognitive impairment (aMCI), a transition stage between normal aging and AD. Accordingly, in the present study we measured the levels of HSPs in hippocampus, inferior parietal lobule (IPL) and cerebellum of subjects with aMCI. The results show a general induction of HSPs and decreased levels of Thioredoxin 1 in aMCI brain suggesting that alteration in the chaperone protein systems might contribute to the pathogenesis and progression of AD. The results also are consistent with the notion that targeting HSP could be a therapeutic approach to delay the progression of aMCI to AD.
Di Domenico
Fabio
F
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
Sultana
Rukhsana
R
Tiu
Georgianne F
GF
Scheff
Nicole N
NN
Perluigi
Marzia
M
Cini
Chiara
C
Butterfield
D Allan
DA
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D018834:Chaperonin 60 / Q000378:metabolism; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000145:classification / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D013879:Thioredoxins / Q000378:metabolism*
D018834:Chaperonin 60; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C491203:TXN protein, human; D013879:Thioredoxins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1