negative regulation of amyloid precursor protein biosynthetic process

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of amyloid precursor protein (APP), the precursor of amyloid-beta. [GOC:go_curators]

Negative regulation of amyloid precursor protein (APP) biosynthetic process is a complex biological pathway that aims to reduce the production of amyloid-beta (Aβ) peptides, which are the primary constituents of amyloid plaques found in the brains of individuals with Alzheimer's disease. This process involves multiple cellular mechanisms, including transcriptional regulation, post-translational modifications, and proteolytic processing of APP.

Transcriptional regulation involves the control of APP gene expression. Specific transcription factors can bind to the APP gene promoter, either activating or repressing its transcription. Factors that decrease APP transcription, such as the transcription factor REST, contribute to negative regulation.

Post-translational modifications, such as phosphorylation and glycosylation, can also influence APP processing. Specific enzymes can modify APP, affecting its stability, trafficking, and interactions with other proteins, ultimately impacting Aβ production.

Proteolytic processing of APP is the central step in Aβ production. APP undergoes cleavage by two main proteases: β-secretase and γ-secretase. β-secretase initiates the cleavage, generating a soluble fragment and a C-terminal fragment. γ-secretase then cleaves the C-terminal fragment, resulting in Aβ peptides. Negative regulation of this process can involve inhibiting the activity of β-secretase or γ-secretase, reducing the overall production of Aβ peptides.

Several key proteins are involved in the negative regulation of APP biosynthetic process. These include:

- **α-secretase (ADAM10):** This enzyme cleaves APP within the Aβ sequence, generating a soluble fragment and preventing Aβ production.
- **γ-secretase inhibitors:** These compounds target γ-secretase activity, blocking the generation of Aβ peptides.
- **APP-binding proteins:** Some proteins bind to APP, preventing its interaction with β-secretase or influencing its trafficking and degradation.
- **Microtubule-associated proteins:** These proteins can regulate the trafficking and processing of APP within neurons.

By targeting these various mechanisms, interventions aimed at negatively regulating APP biosynthetic process can potentially reduce Aβ production, offering a therapeutic approach to Alzheimer's disease.'
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Proteins (2)

Compounds (11)