This page was produced as an assignment for Genetics 564, an undergraduate capstone course at The University of Wisconsin - Madison.
What is gene ontology?
The Gene Ontology (GO) project was established to provide a set of structured, controlled vocabularies for the scientific community to use in annotating genes, gene products, and sequences [1]. By using the GO database, we can better define proteins by their molecular function, cellular component, and the biological process they're involved in [4].
Where is the APP gene located?
The gene that codes for the Amyloid Precursor Protein (APP) is located in the long arm of chromosome 21 in the 21.3 region. Because of its location on chromosome 21, some individuals with Down Syndrome (trisomy 21) also develop Alzheimer's disease later in life. Researchers believe that this is a result of the duplication of the APP gene, which accelerates the Amyloid Cascade Hypothesis, resulting in early-onset Alzheimer's [2,3].
Where does APP localize?
APP is an integral membrane protein located in the synapse of the neuron. It is localized throughout the central nervous system. APP functions as a cell surface receptor in neurons and is involved in cell mobility, promoting transcription activation of Amyloid Beta (Aβ) and is found throughout the central nervous system [5]. Despite recent developments in the understanding of AD, little is known about the function of APP some evidence suggests that APP is normally involved in neuronal development.
|
What biological processes is APP involved in?
Based on consensus information from the GO database, current research indicates that APP is involved in the biological process that results in the breakdown of APP into Aβ via the Amyloid Cascade Hypothesis [6,7].
Discussion
Learning more about the function of APP can help us identify gaps in knowledge about the protein. This allows us to further develop different ways to think about the protein's role in Alzheimer's and under normal non-disease conditions.
References
[1] The Gene Ontology Consortium. 2008. The Gene Ontology project in 2008. Nucleic Acids Res. 36(Database issue): D440-D444.
[2] Cataldo, A. M., Petanceska, S., Peterhoff, C. M., Terio, N. B., Epstein, C. J., Villar, A., ... & Nixon, R. A. (2003). App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. Journal of Neuroscience, 23(17), 6788-6792.
[3] Rovelet-Lecrux, A., Hannequin, D., Raux, G., Le Meur, N., Laquerrière, A., Vital, A., ... & Dubas, F. (2006). APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nature genetics, 38(1), 24-26.
[4] Gene Ontology Consortium. 2017. http://geneontology.org/
[5] Genetics Home Reference. APP gene – Normal function. [Web]. https://ghr.nlm.nih.gov/gene/APP
[6] Hardy, J. A., & Higgins, G. A. (1992). Alzheimer's disease: the amyloid cascade hypothesis. Science, 256(5054), 184.
[7] Pimplikar, S. 2008. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. The International Journal of Biochemistry & Cell Biology. 41: 1261-1268.
Images:
Figure 1. https://ghr.nlm.nih.gov/gene/APP#
[2] Cataldo, A. M., Petanceska, S., Peterhoff, C. M., Terio, N. B., Epstein, C. J., Villar, A., ... & Nixon, R. A. (2003). App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. Journal of Neuroscience, 23(17), 6788-6792.
[3] Rovelet-Lecrux, A., Hannequin, D., Raux, G., Le Meur, N., Laquerrière, A., Vital, A., ... & Dubas, F. (2006). APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nature genetics, 38(1), 24-26.
[4] Gene Ontology Consortium. 2017. http://geneontology.org/
[5] Genetics Home Reference. APP gene – Normal function. [Web]. https://ghr.nlm.nih.gov/gene/APP
[6] Hardy, J. A., & Higgins, G. A. (1992). Alzheimer's disease: the amyloid cascade hypothesis. Science, 256(5054), 184.
[7] Pimplikar, S. 2008. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. The International Journal of Biochemistry & Cell Biology. 41: 1261-1268.
Images:
Figure 1. https://ghr.nlm.nih.gov/gene/APP#