Browse our APP Proteins (APP)

Human Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. Thirteen of 148 (8.8%) individuals had possible pathogenic APP, PSEN1, or PSEN2 variants, including 2 (15.4%) APP variants, 8 (61.5%) PSEN1 variants, and 3 (23.1%) PSEN2 variants

2. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Abeta peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau.

3. In invasive cells, MT1-MMP endocytosis to the endolysosomal reservoir compartment requires flotillin 1 and flotillin 2.

4. These data demonstrate a key role for proteolysis of the C-terminal of APP by gamma-secretase in neuronal dysfunction in monogenic Alzheimer's disease.

5. a Drosophila Alzheimer's disease (AD) model expressing a secreted form of human amyloid-beta42 peptide showed that it recapitulates key aspects of AD pathology, including neuronal death and impaired long-term memory.

6. Beta-amyloid peptide(1-42) (Abeta1-42) : phosphorylated Tau (p-Tau) ratio has potential for being implemented in the clinical routine for differential diagnosis between AD and other dementias and to distinguish underling pathology such as neurodegenerative disease.

7. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP beta-cleavage and Abeta production.

8. miR-346 plays a role in upregulation of APP in the CNS and participates in maintaining APP regulation of Fe, which is disrupted in late stages of AD.

9. analysis of the interaction between monomeric Abeta40/42 and HSA using surface plasmon resonance spectroscopy

10. Structural dynamics of dipeptides and ABETA (25-35) in aqueous solution were demonstrated

11. We found that individuals with elevated beta-amyloid aggregation had a blunted cerebrovascular response compared to non-elevated individuals

12. in cholinergic neurons from Drosophila, beta-amyloid (Abeta) peptides Abeta40 and Abeta42 both induce an increase in spontaneous activity.

13. These data indicate that the sAbeta1-42 may play a dual role during inflammatory process, wherein, it may be involved in protecting the cells from inflammatory damage due to TNF-alpha.

14. We observed that over-expression of PIEZO1 in HEK293 cells increased cell migration velocity ~10-fold, and both enantiomeric A-beta peptides and GsMTx4 independently inhibited migration, demonstrating involvement of PIEZO1 in cell motility.

15. We found amyloid measures to be sensitive early on in predicting subsequent early tau deposition

16. APP facilitate an early step in thrombus formation when amyloid beta (Abeta) peptides accumulate in cerebral vessel walls or atherosclerotic plaques.

17. The differing patterns in cerebral amyloid angiopathy within individuals may relate to the relative tissue burdens of the two major forms of Abeta, with higher levels of Abeta40 promoting a more 'aggressive' form of CAA, and higher levels of Abeta42(3) favouring a greater plaque burden

18. we provide a novel method to convert standardized uptake value ratios-levels into PET-Abeta phase estimates that can be easily translated into neuropathological phases of Abeta-deposition

19. Influence of the familial Alzheimer's disease-associated T43I mutation on the transmembrane structure and gamma-secretase processing of the C99 peptide

20. results may explain the role of hAChE-S in Abeta deposition and aggregation, as amyloidogenic hAChE-S beta-sheet species might seed Abeta aggregation.

Fruit Fly (Drosophila melanogaster) Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. APPL is essential for visual working memory. Interestingly, this short-term memory declines rapidly with age, and this is accompanied by enhanced processing of APPL in aged flies. Furthermore, reducing secretase-mediated proteolytic processing of APPL can prevent the age-related memory loss, whereas overexpression of the secretases aggravates the aging effect.

2. Results show that Drosophila APPL-RNAi largely mimics transgenic amyloid beta in various phenotypes which include eye degeneration, reduced longevity and motor neuron deficit functions. This is the first report showing comparable phenotypes between APPL and amyloid beta in Alzheimer's disease model of Drosophila.

3. Appl siRNA inhibition in cortex glia resulted in longer sleep and reduced expression of genes involved in glutamate recycling.

4. memory is altered by two connected mechanisms-APPL loss-of-function and amyloid peptide toxicity-revealing in Drosophila a functional interaction between APPL and amyloid peptide.

5. The results of this study showed that increased production of the endogenous Drosophila Amyloid Intracellular Domain (dAICD) caused disruption of circadian rest-activity rhythms during aging.

6. Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes.

7. findings suggest that a normal function of presenilin (PS)is to repress kinesin-1 and dynein motor activity during axonal transport of amyloid precursor protein (APP) vesicles; perturbations of APP/PS transport could contribute to early neuropathology observed in Alzheimer's Disease

8. APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth.

9. Data show that Appl is directly regulated by the Ras/MAPK pathway through a mechanism mediated by PntP2.

10. [review] APP-like proteins are involved in neuronal differentiation, neuritic outgrowth, and synapse formation.

11. Disruption of amyloid protein precursor (APP) proteins and specifically their soluble alpha-cleaved ectodomains can protect against progressive neurodegeneration in vivo.

12. Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-beta production by altering Nicastrin maturation and intracellular localization.

13. accumulation of Ass42 plaques induces JNK signaling in neurons and induction of JNK contributes to Ass42 mediated cell death

14. Findings show that age-related changes in amyloid characteristics may be a trigger for late-onset polyglutamine diseases.

15. in adult flies, APPL is not required for learning but is specifically involved in long-term memory, a long lasting memory whose formation requires de novo protein synthesis and is thought to require synaptic structural plasticity.

16. Abeta42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Abeta42 peptide level, in the absence of APP processing.

17. Data suggest that toxic effects of amyloid beta-peptide aggregation in vivo can therefore be eliminated by sequestration of hydrophobic regions in monomeric peptides, even when these are extremely aggregation prone.

18. APP-Like (APPL) can induce postdevelopmental axonal arborization, which depends critically on a conserved motif in the C-terminus and requires interaction with the Abelson (Abl) tyrosine kinase.

19. Study shows that APP-BP1 specifically binds the intracellular domain of APP-like protein (APPL), APP-BP1 mutation partially suppresses the abnormal macrochaete phenotype of Appl(d), while overexpression of dAPP-BP1 causes abnormal macrochaetes.

20. These data offer insight into the toxicity of Abeta and open new areas for further study into Alzheimer's disease pathogenesis.

Cow (Bovine) Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. This study describes Abeta deposition in 102 clinically characterized cattle brains from animals aged 0 to 20 years, demonstrates certain similarities between Abeta deposition patterns exhibited in cattle brains and those in the human brain in early stages of aging

2. release and aggregation of amyloid beta-peptide from brain lipid bilayers is regulated by cholesterol and GM1

Pig (Porcine) Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. APPsw mutation for Alzheimer's disease is not associated with object recognition.

2. Amyloid-beta inhibits No-cGMP signaling in a CD36- and CD47-dependent manner

3. These experiments demonstrate the roles of Chol and ApoE in the modulation of membrane insertion of APP.

4. Two novel transcript variants of porcine APP have been identified, producing isoforms of 695 and 751 amino acids, respectively.

5. APP could be acting through a semaphorin receptor as well

Mouse (Murine) Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. show a novel function for Par3 in regulating polarized convergence between APP and BACE1 in hippocampal neurons

2. Proteasome inhibition precludes APP axonal transport by enhancing its endo-lysosomal delivery, where beta-cleavage is induced.

3. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP beta-cleavage and Abeta production.

4. App(-/-) mice have higher levels of insulin-degrading enzyme (IDE) mRNA, protein, and activity. Regulation of IDE by APP was widespread across numerous tissues, including liver, skeletal muscle, and brain as well as cell types within neural tissue. App-/- mice failed to develop impairment of glucose tolerance on a high-fat, high-sucrose diet.

5. The findings demonstrate that chronic noise exposure exacerbated Alzheimer's disease-like neuropathology, possibly by disrupting Wnt signaling and triggering aberrant tau hyperphosphorylation and amyloid beta peptides in the prefrontal cortex and hippocampus.

6. A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-beta oligomers.

7. Together these data indicate that ONA induces APP expression and that gamma-secretase cleavage of APP releases AICD, which upregulates JNK3 leading to RGC death. This pathway may be a novel target for neuronal protection in optic neuropathies and other forms of neurotrauma.

8. In addition to regulating aspects of neuronal metabolism, APP is an important regulator of whole body energy expenditure and glucose homeostasis under high fat feeding conditions.

9. These findings indicate that under physiological conditions, expression of APP in cerebral vascular endothelium plays an important protective function by maintaining constitutive expression of eNOS .

10. NRBF2 plays an important role in regulating degradation of APP-C-terminal fragments through modulating autophagy.

11. These results provide evidence that both central circadian rhythms and local clock function influence Abeta dynamics and plaque formation.

12. These data identified APP and APLP2 as modulators of normal myelination and demyelination/remyelination conditions.

13. these findings suggest that endogenous Abeta is involved in memory forgetting in the normal brain.

14. pterostilbene attenuated the neuroinflammatory response induced by Abeta1-42 in microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway, indicating that pterostilbene might be an effective therapy for AD.

15. Abeta40 and Abeta42 demonstrated distinct distribution kinetics in plasma and brain compartments, and insulin differentially modulated their distribution.

16. APP/GBR complex formation links presynaptic GBR trafficking to Abeta formation.

17. APP knockout increases synaptic GluA1, PSD-95 and synaptophysin expression and reduces drebrin expression.

18. data indicate that Drp1 is a direct target of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Abeta1-42 induced mitochondrial fission and neuronal toxicity.

19. miR98 reduced the production of Abeta and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in Alzheimer's disease mice.

20. Heme and Hb suppress immune activity of primary mouse astrocytes by reducing expression of several proinflammatory cytokines (e.g. RANTES (regulated on activation normal T cell expressed and secreted)) and the scavenger receptor CD36 and reducing internalization of Abeta(1-42) by astrocytes.

Zebrafish Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. Amyloid beta precursor protein and prion protein have a conserved interaction affecting cell adhesion and central nervous system development.

2. A reduction in app levels causes defective axonal outgrowth of facial branchiomotor and spinal motor neurons, which involves disorganized axonal cytoskeletal elements.

3. these results indicate the Appa-RFP and Aplp2 fusion proteins are likely secreted from the central nervous system and accumulate in the embryonic veins independent of blood flow.

4. expression pattern during embryonic development

5. Data show that knock down of APP in zebrafish results in fish with reduced body length and a short, curly tail, and that wild-type human APP rescues the morphant phenotype, but the Swedish mutant APP, which causes familial AD (fAD), does not.

Xenopus laevis Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. Report of biosynthesis of APP in physiological context and illuminate occurrence of two pools of APP, one of which is linked to neuroendocrine cell activation.

2. A "CAGA" sequence proximal to the "ATG" start codon & immediately upstream of an interleukin-1-responsive element was found in a location unique to APP genes of amyloid plaque-forming species & absent in all other genes surveyed.

3. endogenous cleavages at prohormone convertase-like sites in APP

Rabbit Amyloid beta (A4) Precursor Protein (APP) interaction partners

1. amyloid and oxidative stress-related disease proteins like Alzheimer A beta peptide are increased in expression and form localized accumulations in diabetic muscle in this rabbit model of diabetes.

2. study suggests that hypercholesterolemia-induced Abeta accumulation may be mediated by 27-hydroxycholesterol, involving IGF-1 signaling