Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease
2003; Elsevier BV; Volume: 35; Issue: 11 Linguagem: Inglês
10.1016/s1357-2725(03)00133-x
ISSN1878-5875
AutoresLing Yan, Kevin Morgan, Noor Kalsheker,
Tópico(s)Prion Diseases and Protein Misfolding
ResumoThe processing of amyloid precursor protein (APP) generates amyloid-β (Aβ) peptides 1–40 and 1–42. The latter is neurotoxic and its accumulation results in amyloid fibril formation and the generation of senile plaques, the hallmark of Alzheimer's disease (AD). Whilst there has been considerable progress made in understanding the generation of Aβ by α-, β- and γ-secretase activity on APP, recently enzymes involved in the degradation of Aβ have been identified including neprilysin and insulin-degrading enzyme (IDE). We review the pathways involved in proteolytic processing of APP and discuss the potential implications of aberrant proteolysis on neurodegeneration. It is conceivable that single nucleotide polymorphisms (SNPs) in the regulatory regions of genes in these proteolytic cascades, which alter their expression, could contribute to some of the age-related changes seen in AD.
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