Accumulation of clumps of misfolded or disordered proteins
Misfolded proteins can form protein aggregates or amyloid fibrils, get degraded, or refold back to its native structure.
In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly.[1][2] Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease.[3][4]
After synthesis, proteins typically fold into a particular three-dimensional conformation that is the most thermodynamically favorable: their native state.[5] This folding process is driven by the hydrophobic effect: a tendency for hydrophobic (water-fearing) portions of the protein to shield themselves from the hydrophilic (water-loving) environment of the cell by burying into the interior of the protein. Thus, the exterior of a protein is typically hydrophilic, whereas the interior is typically hydrophobic.
Protein structures are stabilized by non-covalent interactions and disulfide bonds between two cysteine residues. The non-covalent interactions include ionic interactions and weak van der Waals interactions. Ionic interactions form between an anion and a cation and form salt bridges that help stabilize the protein. Van der Waals interactions include nonpolar interactions (i.e. London dispersion force) and polar interactions (i.e. hydrogen bonds, dipole-dipole bond). These play an important role in a protein's secondary structure, such as forming an alpha helix or a beta sheet, and tertiary structure. Interactions between amino acid residues in a specific protein are very important in that protein's final structure.
When there are changes in the non-covalent interactions, as may happen with a change in the amino acid sequence, the protein is susceptible to misfolding or unfolding. In these cases, if the cell does not assist the protein in re-folding, or degrade the unfolded protein, the unfolded/misfolded protein may aggregate, in which the exposed hydrophobic portions of the protein may interact with the exposed hydrophobic patches of other proteins.[6][7] There are three main types of protein aggregates that may form: amorphous aggregates, oligomers, and amyloid fibrils.[8]
^Aguzzi A, O'Connor T (March 2010). "Protein aggregation diseases: pathogenicity and therapeutic perspectives". Nature Reviews. Drug Discovery. 9 (3): 237–248. doi:10.1038/nrd3050. PMID 20190788. S2CID 5756683.
^Stefani M, Dobson CM (November 2003). "Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution". Journal of Molecular Medicine. 81 (11): 678–699. doi:10.1007/s00109-003-0464-5. PMID 12942175. S2CID 23544974.
^De Felice FG, Vieira MN, Meirelles MN, Morozova-Roche LA, Dobson CM, Ferreira ST (July 2004). "Formation of amyloid aggregates from human lysozyme and its disease-associated variants using hydrostatic pressure". FASEB Journal. 18 (10): 1099–1101. doi:10.1096/fj.03-1072fje. PMID 15155566. S2CID 13647147.
^Tanzi RE, Bertram L (February 2005). "Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective". Cell. 120 (4): 545–555. doi:10.1016/j.cell.2005.02.008. PMID 15734686. S2CID 206559875.
^Brüning A, Jückstock J (2015-01-01). "Misfolded proteins: from little villains to little helpers in the fight against cancer". Frontiers in Oncology. 5: 47. doi:10.3389/fonc.2015.00047. PMC 4338749. PMID 25759792.
In molecular biology, proteinaggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump...
Computational methods that use protein sequence and/ or protein structure to predict proteinaggregation. The table below, shows the main features of...
structure prediction can be found at List of protein structure prediction software. Proteinaggregation diseases such as Alzheimer's disease and Huntington's...
Dobson CM (July 2005). "Prediction of "aggregation-prone" and "aggregation-susceptible" regions in proteins associated with neurodegenerative diseases"...
are dyes used for histology staining and biophysical studies of proteinaggregation. For example, thioflavin T is used in the RT-QuIC technique to detect...
Look up aggregation in Wiktionary, the free dictionary. Aggregation may refer to: Aggregation problem (economics) Purchasing aggregation, the joining of...
yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and proteinaggregation. This has been...
merely a reflection of the loss of protein homeostasis, the balance between synthesis, folding, aggregation and protein turnover. Recently the European Medicines...
potentially toxic aggregates. Misfolded proteins, if left unchecked, can lead to aggregation that prevents the protein from moving into its proper conformation...
transmembrane protein is too thin to match the hydrophobic bilayer thickness (right part of Figure), again this might result in proteinaggregation, or changes...
electrostatic forces form when proteins are dissolved in an electrolyte solution. These repulsive forces between proteins prevent aggregation and facilitate dissolution...
Sulfenic acids form disulfides with another protein sulfhydryl group, causing cross-linking and aggregation of proteins. Sulfinic acid and R−S(=O)2−OH derivatives...
of proper protein conformation (shape) and prevention of unwanted proteinaggregation. By helping to stabilize partially unfolded proteins, HSPs aid in...
PMID 16313516. S2CID 24329326. Ross CA, Poirier MA (July 2004). "Proteinaggregation and neurodegenerative disease". Nat. Med. 10 (7): S10–7. doi:10.1038/nm1066...
other nerves are compromised by proteinaggregation and/or amyloid fibril formation. The aggregation of one precursor protein leads to peripheral neuropathy...
platelets do express tissue factor protein and carry both tissue factor pre-mRNA and mature mRNA. Platelet aggregation begins minutes after activation,...
embryogenesis abundant proteins (LEA proteins) are proteins in plants, and some bacteria and invertebrates, that protect against proteinaggregation due to desiccation...
Both are used for histology staining and biophysical studies of proteinaggregation. In particular, these dyes have been used since 1989 to investigate...
associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders...
as molecular chaperone that primarily binds misfolded proteins to prevent proteinaggregation, as well as inhibit apoptosis and contribute to intracellular...
late age of onset – in these cases, the proteinaggregation may be associated with aging-related decline in protein regulation. Some medical treatments are...
PMID 15961430. < Oates, Katherine (2006). "Rheopexy of synovial fluid and proteinaggregation". Journal of the Royal Society Interface. 3 (6): 167–74. doi:10.1098/rsif...
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