Proteopathy
|
WikiDoc Resources for Proteopathy |
|
Articles |
|---|
|
Most recent articles on Proteopathy Most cited articles on Proteopathy |
|
Media |
|
Powerpoint slides on Proteopathy |
|
Evidence Based Medicine |
|
Clinical Trials |
|
Ongoing Trials on Proteopathy at Clinical Trials.gov Clinical Trials on Proteopathy at Google
|
|
Guidelines / Policies / Govt |
|
US National Guidelines Clearinghouse on Proteopathy
|
|
Books |
|
News |
|
Commentary |
|
Definitions |
|
Patient Resources / Community |
|
Patient resources on Proteopathy Discussion groups on Proteopathy Patient Handouts on Proteopathy Directions to Hospitals Treating Proteopathy Risk calculators and risk factors for Proteopathy
|
|
Healthcare Provider Resources |
|
Causes & Risk Factors for Proteopathy |
|
Continuing Medical Education (CME) |
|
International |
|
|
|
Business |
|
Experimental / Informatics |
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Proteopathy (Proteo- [pref. protein]; -pathy [suff. disease]; proteopathies pl.; proteopathic adj.). Proteopathy is the abnormal accumulation and toxicity of proteins in certain disease states.[1] The proteopathies (sometimes referred to as "proteinopathies") comprise more than 30 diseases that affect a variety of organs and tissues, including Alzheimer's disease, Parkinson's disease, type 2 diabetes, amyloidosis, selective hyperproteolytic diseases (e.g. critical illness myopathies or tumor cachexia), and a wide range of other disorders (see Table).[2][3][4][5][6][7]
The proteopathies also are called protein conformational diseases,[6] because a change in the 3-dimensional folding (conformation) of a protein increases the tendency of the protein to misfold and polymerize into aggregates that are resistant to clearance, and can become pathogenic. Because of the common structure of the polypeptide backbone, all proteins have the potential to misfold under some conditions.[8]
Only certain proteins are linked to proteopathy, possibly due to instability or other structural features of the monomeric protein that increase the probability of misconformation,[6][8] which in nearly all instances involves an increase in beta-sheet secondary structure.[8][6][9] Potential risk factors for proteopathic diseases augment the tendency of vulnerable proteins to self-assemble. They include destabilizing changes in the primary amino acid sequence of the protein, post-translational modifications (such as hyperphosphorylation), changes in temperature or pH, an increase in production of a protein, or a decrease in its clearance.[6][8][1] Advancing age frequently is a risk factor.[1]
In some proteopathies, abnormal assembly can be templated on an exogenous protein, typically a misfolded form of the same protein.[10][11] In this way, the disease state can be induced in a susceptible host by the introduction of diseased tissue extract from an afflicted donor. The best known form of such infectious (or transmissible) proteopathy is prion disease, which can be transmitted by exposure of a host organism to purified prion protein in a disease-causing conformation.[12][13] There is now evidence that other proteopathies are inducible by a similar mechanism, including AA amyloidosis, apolipoprotein AII amyloidosis, and Aβ amyloidosis.[11][14] In all of these instances, an aberrant form of the protein itself appears to be the pathogenic agent.
References
- ↑ 1.0 1.1 1.2 Walker LC and LeVine H (2000). "The cerebral proteopathies". Neurobiol Aging. 21: 559–561. PMID 10924770.
- ↑ Walker LC, LeVine III H (2000). "The cerebral proteopathies: Neurodegenerative disorders of protein conformation and assembly". Mol Neurobiol. 21: 83–95. PMID 11327151.
- ↑ Chiti F, Dobson CM (2006). "Protein misfolding, functional amyloid, and human disease". Ann Rev Biochem. 75: 333–366. PMID 16756495.
- ↑ Friedrich O (2006). "Critical illness myopathy: what is happening?". Curr Opin Clin Nutr Metab Care. 9: 403–409. PMID 16778569.
- ↑ Spinner NB (2000). "CADASIL: Notch signaling defect or protein accumulation problem?". J Clin Invest. 105: 561–562. PMID 10712425.
- ↑ 6.0 6.1 6.2 6.3 6.4 Carrell RW, Lomas DA (1997). "Conformational disease". Lancet. 350: 134–138. PMID 9228977.
- ↑ Westermark P (2005). "Aspects on human amyloid forms and their fibril polypeptides". FEBS J. 272: 5942–5949. PMID 16302959.
- ↑ 8.0 8.1 8.2 8.3 Dobson CM (1999). "Protein misfolding, evolution and disease". TIBS. 24: 329–332. PMID 10470028.
- ↑ Selkoe DJ (2003 id = PMID 14685251). "Folding proteins in fatal ways". Nature. 426: 900–904. Check date values in:
|year=(help) - ↑ Hardy J (2005). "Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: 'permissive templating' as a general mechanism underlying neurodegeneration". Biochem Soc Trans. 33: 578–581. PMID 16042548.
- ↑ 11.0 11.1 Walker LC, LeVine H, Mattson MP, Jucker M (2006). "Inducible proteopathies". TINS. 29: 438–443. PMID 16806508.
- ↑ Prusiner SB (2001). "Shattuck lecture—Neurodegenerative diseases and prions". N Engl J Med. 344: 1516–1526. PMID 11357156.
- ↑ Zou WQ, Gambetti P (2005). "From microbes to prions: the final proof of the prion hypothesis". Cell. 121: 155–157. PMID 15851020.
- ↑ Meyer-Luehmann M; et al. (2006). "Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host". Science. 313: 1781–1784. PMID 16990547.
- ↑ Guo L, Salt TE, Luong V, Wood N, Cheung W, Maass A, Ferrari G, Russo-Marie F, Sillito AM, Cheetham ME, Moss SE, Fitzke FW, Cordeiro MF (2007). "Targeting amyloid-beta in glaucoma treatment". PNAS. 104: 13444–13449. PMID 17684098.
- ↑ Quinlan RA, Brenner M, Goldman JE, Messing A (2007). "GFAP and its role in Alexander disease". Exp Cell Res. 313: 2077–2087. PMID 17498694.