regulation of amyloid fibril formation

Definition

Target type: biologicalprocess

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

The regulation of amyloid fibril formation is a complex and multifaceted process involving a delicate interplay of factors that influence the formation, aggregation, and deposition of these proteinacious structures. Amyloid fibrils are highly ordered, insoluble protein aggregates characterized by a cross-beta sheet structure, which can accumulate in various tissues and organs, contributing to a range of debilitating diseases, including Alzheimer's disease, Parkinson's disease, and type II diabetes.

The formation of amyloid fibrils typically begins with the misfolding of a protein or peptide, leading to the exposure of hydrophobic residues that favor aggregation. These misfolded proteins can then interact with each other, forming oligomers that can further assemble into larger amyloid fibrils. The process of fibril formation is often influenced by a number of factors, including:

* **Protein sequence and conformation:** The primary amino acid sequence and the specific three-dimensional conformation of a protein can significantly affect its propensity to form amyloid fibrils. Certain amino acid sequences, such as those rich in hydrophobic residues, are particularly prone to misfolding and aggregation.

* **Environmental factors:** The cellular environment can influence the formation and deposition of amyloid fibrils. Factors such as pH, temperature, and the presence of specific ions can promote or inhibit the aggregation process. For example, a decrease in pH or an increase in temperature can often accelerate amyloid fibril formation.

* **Molecular chaperones:** These proteins are essential for maintaining protein homeostasis and preventing the aggregation of misfolded proteins. Molecular chaperones bind to misfolded proteins and promote their refolding or degradation, thus inhibiting the formation of amyloid fibrils.

* **Proteases:** These enzymes degrade proteins, including misfolded proteins, and can play a role in preventing amyloid fibril formation. Some proteases are specifically involved in the degradation of amyloid fibrils, contributing to their clearance from tissues.

* **Cellular factors:** Cells possess various mechanisms to regulate amyloid fibril formation. For example, specific cellular pathways can be activated to promote the clearance of amyloid fibrils, or to prevent their formation in the first place.

* **Genetic factors:** Genetic mutations can alter the amino acid sequence of proteins, increasing their propensity to misfold and form amyloid fibrils. These mutations can also affect the expression levels of chaperones, proteases, and other cellular factors involved in regulating amyloid fibril formation.

The regulation of amyloid fibril formation is a dynamic process involving a delicate balance between factors promoting and inhibiting fibril formation. Understanding this intricate interplay is essential for developing effective therapies for amyloid-related diseases. Targeting the specific mechanisms involved in the regulation of amyloid fibril formation could potentially lead to novel approaches for preventing or treating these devastating conditions.'
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Proteins (1)

Compounds (60)