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Updated: Jul 26, 2025
Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease
Jiang Chen1,2, Jun-Sheng Chen1,2, Song Li3
1Key Laboratory of Endemic and Ethnic Diseases, Laboratory of Molecular Biology, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China.
Abstract:
Decades of research have demonstrated an incontrovertible role of amyloid-β (Aβ) in the etiology of Alzheimer's disease (AD). However, the overemphasis on the pathological impacts of Aβ may obscure the role of its metabolic precursor, amyloid precursor protein (APP), as a significant hub in the occurrence and progression of AD. The complicated enzymatic processing, ubiquitous receptor-like properties, and abundant expression of APP in the brain, as well as its close links with systemic metabolism, mitochondrial function and neuroinflammation, imply that APP plays multifaceted roles in AD. In this review, we briefly describe the evolutionarily conserved biological characteristics of APP, including its structure, functions and enzymatic processing. We also discuss the possible involvement of APP and its enzymatic metabolites in AD, both detrimental and beneficial. Finally, we describe pharmacological agents or genetic approaches with the capability to reduce APP expression or inhibit its cellular internalization, which can ameliorate multiple aspects of AD pathologies and halt disease progression. These approaches provide a basis for further drug development to combat this terrible disease.
Insights
Amyloid precursor protein (APP) plays a crucial role in Alzheimer's disease (AD) progression, beyond just its metabolite amyloid-beta (Aβ). Targeting APP offers new therapeutic strategies for AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) research has focused heavily on amyloid-beta (Aβ).
- The role of amyloid precursor protein (APP), Aβ's metabolic precursor, in AD etiology is often overlooked.
- APP's complex processing, receptor functions, and links to metabolism, mitochondria, and neuroinflammation suggest multifaceted roles in AD.
Purpose of the Study:
- To review the biological characteristics of APP, including its structure, functions, and processing.
- To discuss the dual role (detrimental and beneficial) of APP and its metabolites in AD.
- To explore therapeutic strategies targeting APP for AD treatment.
Main Methods:
- Review of existing scientific literature on APP and Alzheimer's disease.
- Analysis of APP's biological characteristics and enzymatic processing pathways.
- Discussion of potential therapeutic interventions targeting APP expression and internalization.
Main Results:
- APP exhibits conserved biological characteristics and complex enzymatic processing.
- APP and its metabolites have both detrimental and beneficial roles in AD pathogenesis.
- Pharmacological and genetic approaches targeting APP show promise in ameliorating AD pathologies.
Conclusions:
- APP is a significant factor in Alzheimer's disease occurrence and progression.
- Targeting APP expression or internalization offers a promising therapeutic avenue for AD.
- Further drug development focused on APP is warranted to combat Alzheimer's disease.
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