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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 amyloidosis.[11][14] In all of these instances, an aberrant form of the protein itself appears to be the pathogenic agent.

Proteopathy Major aggregating protein
Alzheimer's disease Amyloid β peptide (); Tau protein (see tauopathies)
Cerebral β-amyloid angiopathy Amyloid β peptide ()
Retinal ganglion cell degeneration in glaucoma[15] Amyloid β peptide ()
Prion diseases (multiple) Prion protein
Parkinson's disease and other synucleinopathies (multiple) α-Synuclein
Tauopathies (multiple) Microtubule-associated protein tau (Tau protein)
Frontotemporal lobar degeneration (FTLD) (Ubi+, Tau-) TDP-43
Amyotrophic lateral sclerosis (ALS) Superoxide dismutase, TDP-43
Huntington's disease and other triplet repeat disorders (multiple) Proteins with tandem glutamine expansions
Familial British dementia ABri
Familial Danish dementia ADan
Hereditary cerebral hemorrhage with amyloidosis (Icelandic) (HCHWA-I) Cystatin C
Alexander Disease[16] Glial fibrillary acidic protein (GFAP)
Familial amyloidotic neuropathy, Senile systemic amyloidosis Transthyretin
Serpinopathies (multiple) Serpins
AL (light chain) amyloidosis (primary systemic amyloidosis) Monoclonal immunoglobulin light chains
AH (heavy chain) amyloidosis Immunoglobulin heavy chains
AA (secondary) amyloidosis Amyloid A protein
Type II diabetes Islet amyloid polypeptide (IAPP; amylin)
Aortic medial amyloidosis Medin (lactadherin)
ApoAI amyloidosis Apolipoprotein AI
ApoAII amyloidosis Apolipoprotein AII
ApoAIV amyloidosis Apolipoprotein AIV
Finnish hereditary amyloidosis Gelsolin
Lysozyme amyloidosis Lysozyme
Fibrinogen amyloidosis Fibrinogen
Dialysis amyloidosis Beta-2 microglobulin
Inclusion body myositis/myopathy Amyloid β peptide ()
Cataracts Crystallins
Medullary thyroid carcinoma Calcitonin
Cardiac atrial amyloidosis Atrial natriuretic factor
Pituitary prolactinoma Prolactin
Hereditary lattice corneal dystrophy Keratoepithelin
Cutaneous lichen amyloidosis Keratins
Corneal lactoferrin amyloidosis Lactoferrin
Pulmonary alveolar proteinosis Surfactant protein C (SP-C)
Critical illness myopathy (CIM) Hyperproteolytic state of myosin ubiquitination


  1. 1.0 1.1 1.2 Walker LC and LeVine H (2000). "The cerebral proteopathies". Neurobiol Aging. 21: 559–561. PMID 10924770.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. Walker LC, LeVine III H (2000). "The cerebral proteopathies: Neurodegenerative disorders of protein conformation and assembly". Mol Neurobiol. 21: 83–95. PMID 11327151.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. Chiti F, Dobson CM (2006). "Protein misfolding, functional amyloid, and human disease". Ann Rev Biochem. 75: 333–366. PMID 16756495.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. Friedrich O (2006). "Critical illness myopathy: what is happening?". Curr Opin Clin Nutr Metab Care. 9: 403–409. PMID 16778569.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. Spinner NB (2000). "CADASIL: Notch signaling defect or protein accumulation problem?". J Clin Invest. 105: 561–562. PMID 10712425.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. 6.0 6.1 6.2 6.3 6.4 Carrell RW, Lomas DA (1997). "Conformational disease". Lancet. 350: 134–138. PMID 9228977.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Westermark P (2005). "Aspects on human amyloid forms and their fibril polypeptides". FEBS J. 272: 5942–5949. PMID 16302959.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. 8.0 8.1 8.2 8.3 Dobson CM (1999). "Protein misfolding, evolution and disease". TIBS. 24: 329–332. PMID 10470028.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  9. Selkoe DJ (2003 id = PMID 14685251). "Folding proteins in fatal ways". Nature. 426: 900–904. Check date values in: |year= (help)<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  10. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  11. 11.0 11.1 Walker LC, LeVine H, Mattson MP, Jucker M (2006). "Inducible proteopathies". TINS. 29: 438–443. PMID 16806508.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  12. Prusiner SB (2001). "Shattuck lecture—Neurodegenerative diseases and prions". N Engl J Med. 344: 1516–1526. PMID 11357156.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  13. Zou WQ, Gambetti P (2005). "From microbes to prions: the final proof of the prion hypothesis". Cell. 121: 155–157. PMID 15851020.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  14. Meyer-Luehmann M; et al. (2006). "Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host". Science. 313: 1781–1784. PMID 16990547.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  15. 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.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  16. Quinlan RA, Brenner M, Goldman JE, Messing A (2007). "GFAP and its role in Alexander disease". Exp Cell Res. 313: 2077–2087. PMID 17498694.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

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