Amyloid fibril formation pathway

General description

Certain soluble peptide and protein, under specific conditions, can aggregate into insoluble forms, which contributes to pathological conditions (Chiti & Dobson, 2006)⁠. The formation of Abeta plagues, a landmark of AD, is a result of the cleavage of Amyloid precursor protein (APP).

APP, plays important developmental roles (Loffler & Huber, 1992)⁠. In adult brain, the expression of APP seems to associate with cell injury (Graham et al., 1996)⁠

References:
  • Chiti, F., & Dobson, C. M. (2006). Protein misfolding, functional amyloid, and human disease. Annual Review of Biochemistry, 75, 333–366. doi:10.1146/annurev.biochem.75.101304.123901
  • Graham, D. I., Gentleman, S. M., Nicoll, J. A., Royston, M. C., McKenzie, J. E., Roberts, G. W., & Griffin, W. S. (1996). Altered beta-APP metabolism after head injury and its relationship to the aetiology of Alzheimer’s disease. Acta Neurochirurgica. Supplement, 66, 96–102.
  • Loffler, J., & Huber, G. (1992). Beta-amyloid precursor protein isoforms in various rat brain regions and during brain development. Journal of Neurochemistry, 59, 1316–1324.
Reactome REACT_75876
KEGG pathway
05010

 
Involvement in Alzheimer's disease
Abeta is the major constitute of amyloid aggregates. To form Abeta, APP is sequentially cleavaged by proteolytic enzyme beta- and gamma-secretase. Among the many cleavage products, Abeta42 is the one most relevant to the disease.
Proteins involved
APP A4_HUMAN
PSEN1 PSN1_HUMAN
PSEN2

PSN2_HUMAN