BACE

Synonyms

Beta-site amyloid precursor protein cleaving enzyme 1, KIAA1149, Asp 2, ASP2, Aspartyl protease 2, BACE, BACE1, Beta-Secretase 1, Membrane-Associated Aspartic Protease 2, Beta-Site APP-Cleaving Enzyme, Memapsin-2, Transmembrane Aspartic Proteinase Asp2, Beta-Site APP-Cleaving Enzyme 1, APP Beta-Secretase, EC 3.4.23.46, HSPC104, EC 3.4.23, Beta-Site APP Cleaving Enzyme 1, Beta-Site Amyloid Beta A4 Precursor Protein-Cleaving Enzyme, Beta-Secretase 1 Precursor Variant 1, EC:3.4.23.46

Description

Beta-secretase 1 (BACE1) responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves CHL1.

KO Status

RenMab: F0

Drug Information

Drugs in clinical trials: 5
Latest Research Phase: Phase 3 Clinical

Drug Name

Code

Phase

Company

Indications

Clinical Trials

BI-1147560

BI-1147560

Suspended

Vitae Pharmaceuticals

Alzheimer Disease

Elenbecestat

E-2609, [14C]E2609

Phase 3 Clinical

Eisai Co Ltd

Alzheimer Disease

Lanabecestat

AZD-3293, LY-3314814

Phase 3 Clinical

Astrazeneca Pharmaceutical Co Ltd

Renal Insufficiency, Hepatic Insufficiency, Alzheimer Disease

Umibecestat

AMG-520, CNP-520

Phase 3 Clinical

Novartis Pharma Ag

Alzheimer Disease

LY-3202626

LY-3202626

Phase 2 Clinical

Eli Lilly And Company

Alzheimer Disease

TAK-070

TAK-070

Phase 1 Clinical

Takeda

Alzheimer Disease

JNJ-67569762

JNJ-67569762

Preclinical

Johnson & Johnson Sa

Alzheimer Disease

LY-2434074

2434074, LY-2434074, LSN-2434074

Discontinued

Eli Lilly And Company

Alzheimer Disease

LY-2811376

LY-2811376

Discontinued

Eli Lilly And Company

Alzheimer Disease

AZD-3839

AZD-3839

Discontinued

Astrazeneca Pharmaceutical Co Ltd

Alzheimer Disease

References


Title

Authors

Source

GGA proteins mediate the recycling pathway of memapsin 2 (BACE)

He X., Li F., Chang W.P., Tang J.,

J. Biol. Chem. 280:11696-11703(2005)

GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network

Wahle T., Prager K., Raffler N., Haass C., Famulok M., Walter J.,

Mol. Cell. Neurosci. 29:453-461(2005)

Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein

Murayama K.S., Kametani F., Saito S., Kume H., Akiyama H., Araki W.,

Eur. J. Neurosci. 24:1237-1244(2006)

Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins

He W., Hu X., Shi Q., Zhou X., Lu Y., Fisher C., Yan R.,

J. Mol. Biol. 363:625-634(2006)

Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme

Spoelgen R., von Arnim C.A., Thomas A.V., Peltan I.D., Koker M., Deng A., Irizarry M.C., Andersen O.M., Willnow T.E., Hyman B.T.,

J. Neurosci. 26:418-428(2006)

A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1

Costantini C., Ko M.H., Jonas M.C., Puglielli L.,

Biochem. J. 407:383-395(2007)

PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1

Jonas M.C., Costantini C., Puglielli L.,

EMBO Rep. 9:916-922(2008)

Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels

Ko M.H., Puglielli L.,

J. Biol. Chem. 284:2482-2492(2009)

Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing

Okada H., Zhang W., Peterhoff C., Hwang J.C., Nixon R.A., Ryu S.H., Kim T.W.,

FASEB J. 24:2783-2794(2010)

Ubiquitin regulates GGA3-mediated degradation of BACE1

Kang E.L., Cameron A.N., Piazza F., Walker K.R., Tesco G.,

J. Biol. Chem. 285:24108-24119(2010)