Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons exposed to oxidative stress.
Recently, we showed that oxidative stress activates the expression and activity of the beta-site AbetaPP-cleaving enzyme (BACE), an aspartyl protease responsible for the beta-secretase cleavage of AbetaPP. The identification of compounds able to prevent the induction of this event is an important goal of therapeutic strategies for Alzheimer's disease (AD). Dehydroepiandrosterone (DHEA) is an adrenal steroid that improves a variety of functions in the central nervous system. Moreover, a series of evidence suggests that DHEA displays antioxidant properties in different experimental models. In the present paper we show that pretreatment with DHEA is able to rescue the increase of mRNA expression, protein levels, and activity of BACE, produced by oxidative stress in NT2 neurons. BACE, being the enzyme that initiates the production of Abeta, is a drug target for AD. Our results imply that DHEA administration may slow down the AD pathological process, lowering Abeta accumulation.
Tamagno
E
E
Department of Experimental Medicine and Oncology, General Pathology Section, University of Torino, Italy. elena.tamagno@unito.it
Guglielmotto
M
M
Bardini
P
P
Santoro
G
G
Davit
A
A
Di Simone
D
D
Danni
O
O
Tabaton
M
M
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D010450:Endopeptidases; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human