Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury.
Amyloid-beta (Abeta) peptides, found in Alzheimer's disease brain, accumulate rapidly after traumatic brain injury (TBI) in both humans and animals. Here we show that blocking either beta- or gamma-secretase, enzymes required for production of Abeta from amyloid precursor protein (APP), can ameliorate motor and cognitive deficits and reduce cell loss after experimental TBI in mice. Thus, APP secretases are promising targets for treatment of TBI.
Loane
David J
DJ
Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
Pocivavsek
Ana
A
Moussa
Charbel E-H
CE
Thompson
Rachel
R
Matsuoka
Yasuji
Y
Faden
Alan I
AI
Rebeck
G William
GW
Burns
Mark P
MP
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000627:therapeutic use*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000172:deficiency; D001930:Brain Injuries / Q000188:drug therapy* / Q000517:prevention & control; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000187:drug effects
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse