Cytoplasmic domain of the β‐amyloid protein precursor of Alzheimer's disease: Function, regulation of proteolysis, and implications for drug development

@article{Kerr2005CytoplasmicDO,
  title={Cytoplasmic domain of the $\beta$‐amyloid protein precursor of Alzheimer's disease: Function, regulation of proteolysis, and implications for drug development},
  author={Megan L Kerr and David Henry Small},
  journal={Journal of Neuroscience Research},
  year={2005},
  volume={80}
}
The β‐amyloid protein precursor (APP) has been extensively studied for its role in amyloid production and the pathogenesis of Alzheimer's disease (AD). However, little is known about the normal function of APP and its biological interactions. In this Mini‐Review, the role of the cytoplasmic domain of APP in APP trafficking and proteolysis is described. These studies suggest that proteins that bind to the cytoplasmic domain may be important targets for drug development in AD. © 2005 Wiley‐Liss… 
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57 Citations
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57 Citations

Insights into the physiological function of the β-amyloid precursor protein: beyond Alzheimer's disease
TLDR
It is concluded that the published data provide strong evidence that APP has a trophic function and is likely to be involved in neural stem cell development, neuronal survival, neurite outgrowth and neurorepair.
The Function of the Amyloid Precursor Protein Family
TLDR
This review will summarize the key activities associated with APP and its paralogues the amyloid precursor like proteins 1 and 2 (APLP1 and APLP2, respectively).
REVIEW: Pin1 in Alzheimer's disease
TLDR
The role of Pin1 is discussed, which is found to be oxidatively modified and to have reduced activity in the hippocampus in mild cognitive impairment (MCI) and AD, and the discovery that this protein is one of the oxidized proteins common to both MCI and AD brain.
Trafficking and proteolytic processing of amyloid precursor protein and secretases in Alzheimer's disease development: An up-to-date review.
Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of lysine 688
TLDR
It is shown that ubiquilin-1 inhibits the maturation of APP by sequestering it in the early secretory pathway, primarily within the Golgi apparatus, with important consequences for the pathogenesis of late-onset AD.
Protein Phosphorylation is a Key Mechanism in Alzheimer's Disease.
TLDR
This review focuses on some of the major protein kinases and protein phosphatases relevant to AD and highlights possible convergence points that may contribute to the different AD pathological hallmarks.
Unraveling in vivo Functions of Amyloid Precursor Protein: Insights from Knockout and Knockdown Studies
TLDR
This review focuses on knockout and knockdown approaches that have provided insights into the physiological functions of APP and discusses their advantages and drawbacks.
Activation of neuronal defense mechanisms in response to pathogenic factors triggering induction of amyloidosis in Alzheimer's disease.
TLDR
A new model for etiology of Alzheimer's disease (AD) is presented which postulates early involvement of specialized neuroprotective mechanisms in the pathology of AD and the evidence related to the possibility that protein hyperphosphorylation may be a byproduct of energetic imbalances in AD cells associated with high levels of protein synthesis is reviewed.
Neddylation dysfunction in Alzheimer's disease
TLDR
Evidence suggesting that dysfunction of neddylation is involved in Alzheimer's disease is summarized and reviewed.
APP Gene
  • Biology
    Definitions
  • 2020
TLDR
The APP gene provides instructions for making a protein called amyloid precursor protein, which is found in many tissues and organs, including the brain and spinal cord, and studies suggest that in the brain, it helps direct the movement of nerve cells (neurons) during early development.
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