positive regulation of amyloid fibril formation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of amyloid fibril formation. [GO_REF:0000058, GOC:aruk, GOC:bc, GOC:TermGenie, PMID:23106396]

Positive regulation of amyloid fibril formation is a complex biological process that involves a series of events leading to the formation of amyloid fibrils, which are highly ordered protein aggregates associated with various neurodegenerative diseases. Here's a detailed description of the process:

**1. Protein Misfolding and Aggregation:**
* The process typically begins with misfolded proteins, which have lost their native structure and conformation. This misfolding can be caused by various factors such as mutations, environmental stress, or aging.
* Misfolded proteins tend to aggregate, forming soluble oligomers. These oligomers can be toxic to cells, contributing to disease pathogenesis.

**2. Amyloid Fibril Formation:**
* Soluble oligomers can further assemble into larger structures called amyloid fibrils. These fibrils are characterized by their highly ordered, beta-sheet-rich structure, forming long, insoluble fibers.
* The aggregation process involves a series of steps including nucleation, elongation, and fibril maturation.

**3. Factors Influencing Amyloid Fibril Formation:**
* **Protein Concentration:** Higher protein concentrations favor aggregation and fibril formation.
* **pH:** Changes in pH can alter protein structure and promote misfolding.
* **Temperature:** Elevated temperatures can destabilize protein structure and facilitate aggregation.
* **Metal Ions:** Certain metal ions can bind to proteins and promote aggregation.
* **Mutations:** Mutations in the protein sequence can alter its folding properties and increase its propensity to form fibrils.
* **Molecular Chaperones:** Chaperone proteins are involved in protein folding and can help prevent misfolding and aggregation.
* **Proteases:** Proteases can degrade misfolded proteins and prevent their accumulation.

**4. Positive Regulation:**
* Positive regulation of amyloid fibril formation involves mechanisms that promote or enhance the formation of amyloid fibrils. This can be achieved through various factors, including:
* **Increased protein expression:** Higher levels of the amyloidogenic protein can lead to increased aggregation.
* **Inhibition of chaperone activity:** Reduced chaperone function can allow misfolded proteins to accumulate and aggregate.
* **Mutations that promote aggregation:** Specific mutations can increase the tendency of a protein to misfold and form fibrils.
* **Environmental factors:** Changes in pH, temperature, or the presence of certain metal ions can promote aggregation.

**5. Consequences of Positive Regulation:**
* Positive regulation of amyloid fibril formation can have detrimental consequences, leading to the accumulation of amyloid fibrils in tissues and organs, ultimately contributing to the development of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and type II diabetes.

**6. Therapeutic Targets:**
* Understanding the mechanisms of positive regulation of amyloid fibril formation is crucial for developing therapeutic strategies to prevent or treat amyloid-related diseases. Potential therapeutic targets include:
* Reducing protein expression.
* Enhancing chaperone activity.
* Inhibiting fibril formation.
* Degrading existing fibrils.
* Targeting upstream signaling pathways involved in disease pathogenesis.

In summary, positive regulation of amyloid fibril formation is a complex biological process that involves a series of events promoting the formation of amyloid fibrils, leading to cellular dysfunction and disease pathogenesis. Understanding the mechanisms of positive regulation is crucial for developing effective therapeutic strategies for amyloid-related diseases.'
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Proteins (3)

Compounds (180)