APP

Synonyms

Amyloid intracellular domain 57, APP, Amyloid intracellular domain 59, PN-II, Amyloid-Beta A4 Protein, Beta-Amyloid Peptide, Alzheimer Disease, CTFgamma, ABETA, AAA, PN2, Amyloid beta-Peptides, Beta-CTF, Amyloid Beta Precursor Protein, Cerebral Vascular Amyloid Peptide, Beta-Amyloid Precursor Protein, Beta-Amyloid Peptide(1-40), Beta-Amyloid Peptide(1-42), Amyloid Beta A4 Protein, Alpha-secretase C-terminal fragment, AICD-50, S-APP-alpha, A4, S-APP-beta, Alzheimer disease amyloid protein, Abeta40, Gamma-CTF(59), Abeta42, Gamma-CTF(57), Alpha-CTF, Amyloid intracellular domain 50, AID(59), Gamma-CTF(50), AID(57), Beta-secretase C-terminal fragment, Amyloid-beta precursor protein, Amyloid precursor protein, AD1, AICD-57, Beta-APP42, APPI, Beta-APP40, AID(50), CVAP, AICD-59, Amyloid Beta (A4) Precursor Protein, Peptidase Nexin-II, Protease Nexin-II, PreA4, ABPP, Testicular Tissue Protein Li 2

Description

Beta amyloid A4 protein as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis . Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity. Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons . Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu and Fe to Cu and Fe, respectively. Amyloid-beta protein 42 is a more effective reductant than amyloid-beta protein 40. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. APP42-beta may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).

KO Status

F1 (+/-)

Drug Information

Launched drugs: 9
Drugs in clinical trials: 38
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Sodium Oligomannurarate

GV-971, 971

Approved

Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences, Ocean University Of China

Cognitive Dysfunction, Alzheimer Disease

Chondroitin sulfate A lithium

Taishan Medical University Affiliated Hospital

Florapronol (18F)

18F-FC-119S, 18F-FC-119(S)

Approved

Korea Institute Of Radiological And Medical Sciences, Futurechem

Alzheimer Disease

Inositol

4L6452S749

Approved

Depression, Anxiety, Diabetic Neuropathies

Chondroitin sulfate C lithium

Taishan Medical University Affiliated Hospital

BEY-2153

BEY-2153

Beyondbio Inc

Flutemetamol (18F)

AH-110690, GE-067

Approved

Ge Healthcare

Contrast agents, Alzheimer Disease, Cognitive Dysfunction, Hydrocephalus, Normal Pressure

Florbetapir(18F)

AV-45, MNI-798

Approved

Eli Lilly And Company

Respiration Disorders, Multiple Sclerosis, Skin Diseases, Spasms, Infantile, Alzheimer Disease, Rheumatic Diseases, Parkinson Disease, Cognitive Dysfunction, Diagnostic agents, Eye Diseases, Collagen Diseases, Lewy Body Disease, Hypersensitivity, Neurodegenerative Diseases

Immune Globulin Subcutaneous (Human) (Octapharma)

Approved

Octapharma

Primary Immunodeficiency Diseases, Dermatomyositis, Immunologic Deficiency Syndromes

Immune globulin 10% (Grifols)

KIg-10, TAL-05-0002

Approved

Bayer Ag

Primary Immunodeficiency Diseases, Myasthenia Gravis, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Purpura, Thrombocytopenic, Idiopathic, Coronavirus Disease 2019 (COVID-19), Immunologic Deficiency Syndromes

References


Title

Authors

Source

Phosphorylation of thr(668) in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress-activated protein kinase 1b (Jun N-terminal kinase-3)

Standen C.L., Brownlees J., Grierson A.J., Kesavapany S., Lau K.-F., McLoughlin D.M., Miller C.C.J.,

J. Neurochem. 76:316-320(2001)

A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing

Weidemann A., Eggert S., Reinhard F.B.M., Vogel M., Paliga K., Baier G., Masters C.L., Beyreuther K., Evin G.,

Biochemistry 41:2825-2835(2002)

Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc

Tarr P.E., Roncarati R., Pelicci G., Pelicci P.G., D'Adamio L.,

J. Biol. Chem. 277:16798-16804(2002)

A cell biological perspective on Alzheimer's disease

Annaert W., De Strooper B.,

Annu. Rev. Cell Dev. Biol. 18:25-51(2002)

Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease

Watanabe N., Araki W., Chui D.H., Makifuchi T., Ihara Y., Tabira T.,

FASEB J. 18:1013-1015(2004)

Characterization of the 5'-end region and the first two exons of the beta-protein precursor gene

La Fauci G., Lahiri D.K., Salton S.R., Robakis N.K.,

Biochem. Biophys. Res. Commun. 159:297-304(1989)

Purification of protease nexin II from human fibroblasts

van Nostrand W.E., Cunningham D.D.,

J. Biol. Chem. 262:8508-8514(1987)

Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides

Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.,

Nat. Biotechnol. 21:566-569(2003)

Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease

Tanzi R.E., McClatchey A.I., Lamperti E.D., Villa-Komaroff L., Gusella J.F., Neve R.L.,

Nature 331:528-530(1988)

Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H.,

Nature 331:530-532(1988)