Amyloid Precursor Protein Trafficking, Processing, and Function*

By G. Thinakaran, E. Koo. Journal of Biological Chemistry, 2008

1,157 citations recorded by the source corpus.

Intracellular trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations over the past two decades. APP is the precursor to the amyloid β-protein (Aβ), the 38–43-amino acid residue peptide that is at the heart of the amyloid cascade hypothesis of Alzheimer disease (AD). Tremendous progress has been made since the initial identification of Aβ as the principal component of brain senile plaques of individuals with AD. Specifically, molecular characterization of the secretases involved in Aβ production has facilitated cell biological investigations on APP processing and advanced efforts to model AD pathogenesis in animal models. This minireview summarizes salient features of APP trafficking and amyloidogenic processing and discusses the putative biological functions of APP.

Subfields: Cell Biology, Genetics, Physiology

View Paper: https://www.semanticscholar.org/paper/b12b6bf23f1632f4fed655b84d74ec132d9d0687

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In Cell Biology

1. Ding Xu
2. G. Bu
3. Mark P. Mattson
4. J. Esko
5. M. Gleichmann
6. Vivian W. Chow
7. Philip C. Wong

In Genetics

1. G. Bu
2. Mark P. Mattson
3. J. Esko
4. M. Gleichmann
5. Vivian W. Chow
6. Philip C. Wong

In Physiology

1. G. Bu
2. Mark P. Mattson
3. M. Gleichmann
4. Vivian W. Chow
5. Philip C. Wong
6. M. O’Banion
7. Michael T. Heneka

Citations in the corpus

• Alzheimer's disease risk genes and mechanisms of disease pathogenesis (2014, neutral): “Sequential cleavage of APP, a transmembrane neuronal protein, by β-secretase and then by γ-secretase produces Aβ (23).”
• Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy (2009, background): “Many of the effects of cholesterol on APP processing relate to the important role of cholesterol in lipid rafts, where APP processing by β- and γ-secretase cleavage is favoure”
• An Overview of APP Processing Enzymes and Products (2010, positive): “Keywords Amyloid beta; α-secretase; β-secretase; γ-secretase; APP; AICD Introduction Excess amyloid β-peptide (Aβ) is believed to be a main contributor to the dysfunction and degeneration of neurons that occurs in Alzheimer’s disease (AD) (see Thinakaran and Koo, 2008 for review).”
• Structural conversion of neurotoxic amyloid-β(1–42) oligomers to fibrils (2010, neutral): “Single touch AFM was carried out using a LifeScan controller developed by LifeAFM (Port Jefferson, NY) interfaced with a Digital Instruments (Santa Barbara, CA) MultiMode microscope fitted with an E scanner (see Supplementary Results 2 for full methods).”
• Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases (2015, background): “In this review we briefly examined the evidence of environmental etiologies related to two of the most common neurodegenerative diseases, AD and PD, from epidemiological as well as experimental studies.”
• Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics (2019, background): “Studies with transiently transfected cell lines show that APP moderates cell survival, growth, and motility, along with neurite outgrowth and functions, which are attributed to the release of soluble ectodomains upon normal cleavage of APP.13,14 The importance of APP has been highlighted by studies ”
• Demystifying Heparan Sulfate–Protein Interactions (2014, background): “Amyloid precursor protein (APP) is the precursor for amyloid-β, which accumulates in Alzheimer disease (55).”