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Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease
Abstract
The processing of amyloid precursor protein (APP) generates amyloid-beta (Abeta) 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 Abeta by alpha-, beta- and gamma-secretase activity on APP, recently enzymes involved in the degradation of Abeta 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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“The amyloid-beta peptides can be variable lengths depending on specific cleavage site, but commonly occur as a peptide of either 40 or 42 amino acids.(11)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [11]
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Metadata
- Authors
- Ling, Y., Morgan, K., & Kalsheker, N.
- Affiliations
- University of Nottingham (GB)
- Corresponding author
- Morgan, Kevin
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 35
- Issue
- 11
- Pages
- 1505-1535
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2050373702
- Cited by
- 224
- References
- 315
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 6 · 2023: 11 · 2022: 5 · 2021: 12 · 2020: 3 · 2019: 6 · 2018: 13 · 2017: 8 · 2016: 9 · 2015: 5 · 2014: 14 · 2013: 14 · 2012: 8
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid precursor protein, Alzheimer's disease, amyloid-beta, proteolytic processing, alpha-secretase, beta-secretase, gamma-secretase, neprilysin, insulin-degrading enzyme, amyloid fibril formation, amyloid plaques, neurodegeneration, single nucleotide polymorphisms, gene expression regulation
- MeSH terms
- Alzheimer Disease, Animals, Humans, Endopeptidases, Protein Processing, Post-Translational, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases
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