BACE1 expression and activity: relevance in Alzheimer's disease.
A turning point of research in Alzheimer's disease was undoubtedly the discovery of BACE1, the amyloid-beta precursor protein-cleaving enzyme that initiates the generation of amyloid-beta, the peptide strongly suspected to be responsible for neuronal malfunction and death. Several research groups started a race to identify the best inhibitor of BACE1 activity. On the other hand, basic researchers are evaluating the changes in BACE1 expression and activity with the aim to better understand the pathogenetic process of the disease. Along this second line of research, in the last few years many important results have been reported in various experimental models, as well as in Alzheimer's disease patients. As a consequence, new pathogenetic paradigms have been developed. We have reviewed these reports trying to highlight contrasting viewpoints, data awaiting final confirmation, and promising perspectives.
Zacchetti
Daniele
D
Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Milano, Italy. zacchetti.daniele@hsr.it
Chieregatti
Evelina
E
Bettegazzi
Barbara
B
Mihailovich
Marija
M
Sousa
Vitor Lino
VL
Grohovaz
Fabio
F
Meldolesi
Jacopo
J
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human