Proteins misfolding

Protein Misfolding and Neurodegenerative Disease Therapeutic Opportunities... 

To this list of protein misfolding diseases can be added rare familial amyloidoses in which the mutated proteins have the classic amyloid fibril congophilic birefringence and cross-(3-sheet structure (Table 3). Many of these deposits have an impact on the central nervous system (TTR, cystatin, lysozyme) as well as on other organ systems. A newly described disease, familial British dementia, is associated with the deposition of Abri, a 34 amino acid, 4 kDa peptide cleaved from a 277 amino acid precursor sequence, the last 10 amino acids of which are not normally translated [52]. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is... 

D. Protein Misfolding and Disease Amyloid Fibril Formation. 82... 

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

Dobson CM. Protein misfolding, evolution, and disease. Trends Biochem. Sci. 1999 24 329-332. 

Horwich, A. L., and Weissman, J. S. (1997). Deadly conformations—protein misfolding in prion disease. Cell 89, 499-510. 

Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., and Stefani, M. (2002). Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416, 507-511. 

Kayed, R., Sokolov, Y., Edmonds, B., Mclntire, T. M., Milton, S. C., Hall, J. E., and Glabe, C. G. (2004). Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. /. Biol. Chem. 279, 46363-46366. 

Forloni, G., Terreni, L., Bertani, I., et al. (2002) Protein misfolding in Alzheimer s and Parkinson s disease genetics and molecular mechanisms. NeurobioL Aging, 23, 957-976. 

Cummings CJ, Mancini MA, Antalffy B, DeFranco DB, Orr HT, and Zoghbi HY (1998) Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCAl. Nat. Genet. 19 148-154. 

Substrate modification (phosphorylation, association with, an andUary protein, misfolding, etc.) 9... 

Other protein misfolding-associated diseases include lung diseases such as cystic fibrosis and hereditary emphysema, blood coagulation, certain infectious diseases, and liver diseases. Thus, a better understanding of chain folding is important for our health. 

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