Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of amyloid fibril formation. [GO_REF:0000058, GOC:aruk, GOC:bc, GOC:TermGenie, PMID:23106396]
Negative regulation of amyloid fibril formation is a complex biological process that aims to prevent the formation of harmful amyloid fibrils, which are protein aggregates that can lead to various diseases, including Alzheimer's disease, Parkinson's disease, and type II diabetes. This process involves a diverse array of cellular mechanisms, including:
1. **Chaperone-mediated protein folding:** Chaperones are proteins that assist in the proper folding of newly synthesized proteins, preventing misfolding and aggregation. Molecular chaperones such as heat shock proteins (HSPs) like Hsp70 and Hsp90 directly interact with misfolded proteins, promoting their refolding or targeted degradation.
2. **Proteostasis and degradation pathways:** The ubiquitin-proteasome system (UPS) is a major cellular pathway responsible for degrading misfolded or damaged proteins, preventing their accumulation and aggregation. The UPS targets proteins for degradation through ubiquitination, tagging them with ubiquitin molecules, leading to their breakdown by the proteasome. Other pathways, such as autophagy, also contribute to protein clearance.
3. **Amyloid-specific inhibitors:** Some proteins specifically inhibit amyloid fibril formation by binding to the misfolded protein monomers or oligomers, preventing their aggregation. These inhibitors can include amyloid-binding proteins, such as α-synuclein and tau, which can interact with the aggregating proteins and prevent their assembly into fibrils.
4. **Cellular detoxification mechanisms:** Cells employ detoxification systems, including glutathione S-transferases and metallothioneins, to remove toxic compounds and oxidative stress that can contribute to protein misfolding and aggregation.
5. **Signal transduction pathways:** Specific signal transduction pathways, such as the unfolded protein response (UPR), are activated when cells detect misfolded proteins. The UPR triggers cellular responses, including increased chaperone production, enhanced protein degradation, and ultimately apoptosis if misfolded proteins cannot be resolved.
The intricate interplay of these mechanisms ensures that the balance between protein folding, degradation, and aggregation is maintained, preventing the accumulation of amyloid fibrils and mitigating their detrimental effects. Understanding the molecular details of these pathways offers potential therapeutic targets for diseases associated with amyloid fibril formation.'
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Protein | Definition | Taxonomy |
---|---|---|
Islet amyloid polypeptide | An islet amyloid polypeptide that is encoded in the genome of human. [PRO:DNx, UniProtKB:P10997] | Homo sapiens (human) |
Alpha-crystallin B chain | An alpha-crystallin B chain that is encoded in the genome of human. [PRO:DNx, UniProtKB:P02511] | Homo sapiens (human) |
Low-density lipoprotein receptor | A low-density lipoprotein receptor that is encoded in the genome of human. [PRO:DNx, UniProtKB:P01130] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
25-hydroxycholesterol | 25-hydroxy steroid; oxysterol | human metabolite | |
lanosterol | 14alpha-methyl steroid; 3beta-sterol; tetracyclic triterpenoid | bacterial metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite | |
s 1033 | (trifluoromethyl)benzenes; imidazoles; pyridines; pyrimidines; secondary amino compound; secondary carboxamide | anticoronaviral agent; antineoplastic agent; tyrosine kinase inhibitor | |
morin | morin : A pentahydroxyflavone that is 7-hydroxyflavonol bearing three additional hydroxy substituents at positions 2' 4' and 5. morin: a light yellowish pigment found in the wood of old fustic (Chlorophora tinctoria) | 7-hydroxyflavonol; pentahydroxyflavone | angiogenesis modulating agent; anti-inflammatory agent; antibacterial agent; antihypertensive agent; antineoplastic agent; antioxidant; EC 5.99.1.2 (DNA topoisomerase) inhibitor; hepatoprotective agent; metabolite; neuroprotective agent |