Proteopathy

Micrograph of a section of the cerebral cortex from a patient with Alzheimer's disease, immunostained with an antibody to Aβ (brown), a protein fragment that accumulates in senile plaques and cerebral amyloid angiopathy. 10X microscope objective.

In medicine, proteopathy (Proteo- [pref. protein]; -pathy [suff. disease]; proteopathies pl.; proteopathic adj.) refers to a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body.[1][2] Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a gain of toxic function) or they can lose their normal function.[3] The proteopathies (also known as proteinopathies, protein conformational disorders, or protein misfolding diseases) include such diseases as Creutzfeldt–Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, and a wide range of other disorders (see List of Proteopathies).[2][4][5][6][7][8]

The concept of proteopathy can trace its origins to the mid-19th century, when, in 1854, Rudolf Virchow coined the term amyloid ("starch-like") to describe a substance in cerebral corpora amylacea that exhibited a chemical reaction resembling that of cellulose. In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein.[9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids have in common birefringence in cross-polarized light after staining with the dye Congo Red, as well as a fibrillar ultrastructure when viewed with an electron microscope.[9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of Aβ protein in the brains of Alzheimer patients.[10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign.[11][12]

Pathophysiology

In most, if not all proteopathies, a change in 3-dimensional folding (conformation) increases the tendency of a specific protein to bind to itself.[5] In this aggregated form, the protein is resistant to clearance and can interfere with the normal capacity of the affected organs. In some cases, misfolding of the protein results in a loss of its usual function. For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein,[3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus.[13][14] Because proteins share a common structural feature known as the polypeptide backbone, all proteins have the potential to misfold under some circumstances.[15] However, only a relatively small number of proteins are linked to proteopathic disorders, possibly due to structural idiosyncrasies of the vulnerable proteins. For example, proteins that are normally unfolded or relatively unstable as monomers (that is, as single, unbound protein molecules) are more likely to misfold into an abnormal conformation.[5][15][16] In nearly all instances, the disease-causing molecular configuration involves an increase in beta-sheet secondary structure of the protein.[5][15][17][18] The abnormal proteins in some proteopathies have been shown to fold into multiple 3-dimensional shapes; these variant, proteinaceous structures are defined by their different pathogenic, biochemical, and conformational properties.[19] They have been most thoroughly studied with regard to prion disease, and are referred to as protein strains.[20][21]

Immunostained α-synuclein (brown) in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the cerebral cortex of a patient with Lewy body disease, a synucleinopathy. 40X microscope objective.

The likelihood that proteopathy will develop is increased by certain risk factors that promote the self-assembly of a protein. These 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.[1][5][15] Advancing age is a strong risk factor,[1] as is traumatic brain injury.[22][23] In the aging brain, multiple proteopathies can overlap.[24] For example, in addition to tauopathy and Aβ-amyloidosis (which coexist as key pathologic features of Alzheimer's disease), many Alzheimer patients have concomitant synucleinopathy (Lewy bodies) in the brain.[25]

It is hypothesized that chaperones and co-chaperones (proteins that assist protein folding) may antagonize proteotoxicity during aging and in protein misfolding-diseases to maintain proteostasis.[26][27][28]

Seeded induction

Some proteins can be induced to form abnormal assemblies by exposure to the same (or similar) protein that has folded into a disease-causing conformation, a process called 'seeding' or 'permissive templating'.[29][30] In this way, the disease state can be brought about in a susceptible host by the introduction of diseased tissue extract from an afflicted donor. The best known form of such inducible proteopathy is prion disease,[31] which can be transmitted by exposure of a host organism to purified prion protein in a disease-causing conformation.[32][33] There is now evidence that other proteopathies can be induced by a similar mechanism, including Aβ amyloidosis, amyloid A (AA) amyloidosis, and apolipoprotein AII amyloidosis,[30][34] tauopathy,[35] synucleinopathy,[36][37][38][39] and the aggregation of superoxide dismutase-1 (SOD1),[40][41] polyglutamine,[42][43] and TAR DNA-binding protein-43 (TDP-43).[44]

In all of these instances, an aberrant form of the protein itself appears to be the pathogenic agent. In some cases, the deposition of one type of protein can be experimentally induced by aggregated assemblies of other proteins that are rich in β-sheet structure, possibly because of structural complementarity of the protein molecules. For example, AA amyloidosis can be stimulated in mice by such diverse macromolecules as silk, the yeast amyloid Sup35, and curli fibrils from the bacterium Escherichia coli.[45] In addition, apolipoprotein AII amyloid can be induced in mice by a variety of β-sheet rich amyloid fibrils,[46] and cerebral tauopathy can be induced by brain extracts that are rich in aggregated Aβ.[47] There is also experimental evidence for cross-seeding between prion protein and Aβ.[48] In general, such heterologous seeding is less efficient than is seeding by a corrupted form of the same protein.

List of proteopathies

Proteopathy Major aggregating protein
Alzheimer's disease[16] Amyloid β peptide (Aβ); Tau protein (see tauopathies)
Cerebral β-amyloid angiopathy[49] Amyloid β peptide (Aβ)
Retinal ganglion cell degeneration in glaucoma[50] Amyloid β peptide (Aβ)
Prion diseases (multiple)[51] Prion protein
Parkinson's disease and other synucleinopathies (multiple)[52] α-Synuclein
Tauopathies (multiple)[53] Microtubule-associated protein tau (Tau protein)
Frontotemporal lobar degeneration (FTLD) (Ubi+, Tau-)[54] TDP-43
FTLD–FUS[54] Fused in sarcoma (FUS) protein
Amyotrophic lateral sclerosis (ALS)[55][56] Superoxide dismutase, TDP-43, FUS, C9ORF72, ubiquilin-2 (UBQLN2)
Huntington's disease and other trinucleotide repeat disorders (multiple)[57][58] Proteins with tandem glutamine expansions
Familial British dementia[49] ABri
Familial Danish dementia[49] ADan
Hereditary cerebral hemorrhage with amyloidosis (Icelandic) (HCHWA-I)[49] Cystatin C
CADASIL[59] Notch3
Alexander disease[60] Glial fibrillary acidic protein (GFAP)
Seipinopathies[61] Seipin
Familial amyloidotic neuropathy, Senile systemic amyloidosis Transthyretin[62]
Serpinopathies (multiple)[63] Serpins
AL (light chain) amyloidosis (primary systemic amyloidosis) Monoclonal immunoglobulin light chains[62]
AH (heavy chain) amyloidosis Immunoglobulin heavy chains[62]
AA (secondary) amyloidosis Amyloid A protein[62]
Type II diabetes[64] Islet amyloid polypeptide (IAPP; amylin)
Aortic medial amyloidosis Medin (lactadherin)[62]
ApoAI amyloidosis Apolipoprotein AI[62]
ApoAII amyloidosis Apolipoprotein AII[62]
ApoAIV amyloidosis Apolipoprotein AIV[62]
Familial amyloidosis of the Finnish type (FAF) Gelsolin[62]
Lysozyme amyloidosis Lysozyme[62]
Fibrinogen amyloidosis Fibrinogen[62]
Dialysis amyloidosis Beta-2 microglobulin[62]
Inclusion body myositis/myopathy[65] Amyloid β peptide (Aβ)
Cataracts[66] Crystallins
Retinitis pigmentosa with rhodopsin mutations[67] rhodopsin
Medullary thyroid carcinoma Calcitonin[62]
Cardiac atrial amyloidosis Atrial natriuretic factor[62]
Pituitary prolactinoma Prolactin[62]
Hereditary lattice corneal dystrophy Keratoepithelin[62]
Cutaneous lichen amyloidosis[68] Keratins
Mallory bodies[69] Keratin intermediate filament proteins
Corneal lactoferrin amyloidosis Lactoferrin[62]
Pulmonary alveolar proteinosis Surfactant protein C (SP-C)[62]
Odontogenic (Pindborg) tumor amyloid Odontogenic ameloblast-associated protein[62]
Seminal vesicle amyloid Semenogelin I[62]
Apolipoprotein C2 amyloidosis Apolipoprotein C2 (ApoC2)[62]
Apolipoprotein C3 amyloidosis Apolipoprotein C3 (ApoC3)[62]
Lect2 amyloidosis Leukocyte chemotactic factor-2 (Lect2)[62]
Insulin amyloidosis Insulin[62]
Galectin-7 amyloidosis (primary localized cutaneous amyloidosis) Galectin-7 (Gal7)[62]
Corneodesmosin amyloidosis Corneodesmosin[62]
Enfuvirtide amyloidosis[70] Enfuvirtide[62]
Cystic Fibrosis[71] cystic fibrosis transmembrane conductance regulator (CFTR) protein
Sickle cell disease[72] Hemoglobin

See also

References

  1. 1 2 3 Walker LC, LeVine III H (2000). "The cerebral proteopathies". Neurobiol Aging. 21 (4): 559–561. PMID 10924770. doi:10.1016/S0197-4580(00)00160-3.
  2. 1 2 Walker LC, LeVine III H (2000). "The cerebral proteopathies: Neurodegenerative disorders of protein conformation and assembly". Mol Neurobiol. 21 (1–2): 83–95. PMID 11327151. doi:10.1385/MN:21:1-2:083.
  3. 1 2 Luheshi M, Crowther DC, Dobson CM (2008). "Protein misfolding and disease: from the test tube to the organism". Current Opinion in Chemical Biology. 12 (1): 25–31. PMID 18295611. doi:10.1016/j.cbpa.2008.02.011.
  4. ↑ Chiti F, Dobson CM (2006). "Protein misfolding, functional amyloid, and human disease". Annu Rev Biochem. 75 (1): 333–366. PMID 16756495. doi:10.1146/annurev.biochem.75.101304.123901.
  5. 1 2 3 4 5 Carrell RW, Lomas DA (1997). "Conformational disease". Lancet. 350 (9071): 134–138. PMID 9228977. doi:10.1016/S0140-6736(97)02073-4.
  6. ↑ Westermark P, et al. (2007). "A primer of amyloid nomenclature". Amyloid. 14 (3): 179–183. PMID 17701465. doi:10.1080/13506120701460923.
  7. ↑ Westermark, GT; et al. (2017). "Noncerebral Amyloidoses: Aspects on Seeding, Cross-Seeding, and Transmission". Cold Spring Harb Perspect Med. PMID 28108533. doi:10.1101/cshperspect.a024323.
  8. ↑ Prusiner, SB (2013). "Biology and genetics of prions causing neurodegeneration". Annu Rev Genet. 47: 601–623. PMID 24274755. doi:10.1146/annurev-genet-110711-155524.
  9. 1 2 Sipe JD, Cohen AS (2000). "Review: History of the amyloid fibril". J Struct Biol. 130 (2–3): 88–98. PMID 10940217. doi:10.1006/jsbi.2000.4221.
  10. ↑ Wisniewski HM, Sadowski M, Jakubowska-Sadowska K, Tarnawski M, Wegiel J (1998). "Diffuse, lake-like amyloid-beta deposits in the parvopyramidal layer of the presubiculum in Alzheimer disease". J Neuropath Exp Neurol. 57 (7): 674–683. PMID 9690671. doi:10.1097/00005072-199807000-00004.
  11. ↑ Glabe CG (2006). "Common mechanisms of amyloid oligomer pathogenesis in degenerative disease". Neurobiol Aging. 27 (4): 570–575. PMID 16481071. doi:10.1016/j.neurobiolaging.2005.04.017.
  12. ↑ Gadad BS, Britton GB, Rao KS (2011). "Targeting oligomers in neurodegenerative disorders: lessons from α-synuclein, tau, and amyloid-β peptide". Journal of Alzheimer's disease : JAD. 24 Suppl 2: 223–232. PMID 21460436. doi:10.3233/JAD-2011-110182.
  13. ↑ Ito D, Suzuki N (2011). "Conjoint pathologic cascades mediated by ALS/FTLD-U linked RNA-binding proteins TDP-43 and FUS". Neurology. 77 (17): 1636–43. PMC 3198978 Freely accessible. PMID 21956718. doi:10.1212/WNL.0b013e3182343365.
  14. ↑ Wolozin, B; Apicco, D (2015). "RNA binding proteins and the genesis of neurodegenerative diseases". Adv Exp Med Biol. 822: 11–15. doi:10.1007/978-3-319-08927-0_3.
  15. 1 2 3 4 Dobson CM (1999). "Protein misfolding, evolution and disease". TIBS. 24 (9): 329–332. PMID 10470028. doi:10.1016/S0968-0004(99)01445-0.
  16. 1 2 Jucker, M; Walker, LC (2013). "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases". Nature. 501: 45–51. doi:10.1038/nature12481.
  17. ↑ Selkoe DJ (2003). "Folding proteins in fatal ways". Nature. 426 (6968): 900–904. PMID 14685251. doi:10.1038/nature02264.
  18. ↑ Eisenberg, D; Jucker, M (2012). "The amyloid state of proteins in human diseases". Cell. 148: 1188–1203. doi:10.1016/j.cell.2012.02.022.
  19. ↑ Walker, LC (2016). "Proteopathic Strains and the Heterogeneity of Neurodegenerative Diseases". Ann Rev Genet. 50: 329–346. doi:10.1146/annurev-genet-120215-034943.
  20. ↑ Collinge J, Clarke AR (2007). "A general model of prion strains and their pathogenicity". Science. 318 (5852): 930–936. PMID 17991853. doi:10.1126/science.1138718.
  21. ↑ Colby DW, Prusiner SB (2011). "De novo generation of prion strains". Nature Reviews Microbiology. 9 (11): 771–7. PMID 21947062. doi:10.1038/nrmicro2650.
  22. ↑ DeKosky ST, Ikonomovic MD, Gandy S (2010). "Traumatic brain injury--football, warfare, and long-term effects". New England Journal of Medicine. 363 (14): 1293–1296. PMID 20879875. doi:10.1056/NEJMp1007051.
  23. ↑ McKee, AC; et al. (2015). "The Neuropathology of chronic traumatic encephalopathy". Brain Pathol. 25: 350–364. doi:10.1111/bpa.12248.
  24. ↑ Nelson, PT; et al. (2012). "Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature". J Neuropathol Exp Neurol. 71: 362–381. doi:10.1097/NEN.0b013e31825018f7.
  25. ↑ Mrak RE, Griffin WS (2007). "Dementia with Lewy bodies: Definition, diagnosis, and pathogenic relationship to Alzheimer's disease". Neuropsychiatr Dis Treat. 3 (5): 619–625. PMC 2656298 Freely accessible. PMID 19300591.
  26. ↑ Douglas, P. M.; Summers, D. W.; Cyr, D. M. (2009). "Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways". Prion. 3 (2): 51–58. PMC 2712599 Freely accessible. PMID 19421006. doi:10.4161/pri.3.2.8587.
  27. ↑ Brehme M, et al. (2014). "A conserved chaperome sub-network safeguards protein homeostasis in aging and neurodegenerative disease". Cell Rep. 9: 1135–1150. PMC 4255334 Freely accessible. PMID 25437566. doi:10.1016/j.celrep.2014.09.042.
  28. ↑ Brehme M, Voisine C (2016). "Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity". Dis Model Mech. 9: 823–38. PMC 5007983 Freely accessible. PMID 27491084. doi:10.1242/dmm.024703.
  29. ↑ 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 (Pt 4): 578–581. PMID 16042548. doi:10.1042/BST0330578.
  30. 1 2 Walker LC, LeVine H, Mattson MP, Jucker M (2006). "Inducible proteopathies". TINS. 29 (8): 438–443. PMID 16806508. doi:10.1016/j.tins.2006.06.010.
  31. ↑ Prusiner SB (2001). "Shattuck lecture—Neurodegenerative diseases and prions". N Engl J Med. 344 (20): 1516–1526. PMID 11357156. doi:10.1056/NEJM200105173442006.
  32. ↑ Zou WQ, Gambetti P (2005). "From microbes to prions: the final proof of the prion hypothesis". Cell. 121 (2): 155–157. PMID 15851020. doi:10.1016/j.cell.2005.04.002.
  33. ↑ Ma, J (2012). "The role of cofactors in prion propagation and infectivity". PLoS Pathog. 8: e1002589. doi:10.1371/journal.ppat.1002589.
  34. ↑ Meyer-Luehmann M, et al. (2006). "Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host". Science. 313 (5794): 1781–1784. PMID 16990547. doi:10.1126/science.1131864.
  35. ↑ Clavaguera F, Bolmont T, Crowther RA, et al. (2009). "Transmission and spreading of tauopathy in transgenic mouse brain". Nature Cell Biology. 11 (7): 909–13. PMC 2726961 Freely accessible. PMID 19503072. doi:10.1038/ncb1901.
  36. ↑ Desplats P, et al. (2009). "Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein". Proc. Natl. Acad. Sci. USA. 106 (31): 13010–13015. PMC 2722313 Freely accessible. PMID 19651612. doi:10.1073/pnas.0903691106.
  37. ↑ Hansen C, et al. (2011). "α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells". J Clin Invest. 121 (2): 715–725. PMC 3026723 Freely accessible. PMID 21245577. doi:10.1172/JCI43366.
  38. ↑ Kordower JH, et al. (2011). "Transfer of host-derived alpha synuclein to grafted dopaminergic neurons in rat". Neurobiol Dis. 43 (3): 552–557. PMC 3430516 Freely accessible. PMID 21600984. doi:10.1016/j.nbd.2011.05.001.
  39. ↑ Kordower JH, et al. (2008). "Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease". Nat Med. 14 (5): 504–506. PMID 18391962. doi:10.1038/nm1747.
  40. ↑ Chia R, et al. (2010). Feany MB, ed. "Superoxide Dismutase 1 and tgSOD1G93A Mouse Spinal Cord Seed Fibrils, Suggesting a Propagative Cell Death Mechanism in Amyotrophic Lateral Sclerosis". PLoS ONE. 5: e10627. PMC 2869360 Freely accessible. PMID 20498711. doi:10.1371/journal.pone.0010627.
  41. ↑ Munch C, O'Brien J, Bertolotti A (2011). "Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells". Proc Natl Acad Sci U S A. 108 (9): 3548–3553. PMC 3048161 Freely accessible. PMID 21321227. doi:10.1073/pnas.1017275108.
  42. ↑ Ren PH, et al. (2009). "Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates". Nat Cell Biol. 11 (2): 219–225. PMC 2757079 Freely accessible. PMID 19151706. doi:10.1038/ncb1830.
  43. ↑ Pearce, MM; Kopito, RR (2017). "Prion-like characteristics of polyglutamine-containing proteins". Cold Spring Harb Perspect Med. pii: a024257. doi:10.1101/cshperspect.a024257.
  44. ↑ Furukawa Y, et al. (2011). "A Seeding Reaction Recapitulates Intracellular Formation of Sarkosyl-insoluble Transactivation Response Element (TAR) DNA-binding Protein-43 Inclusions". J Biol Chem. 286 (21): 18664–18672. PMC 3099683 Freely accessible. PMID 21454603. doi:10.1074/jbc.M111.231209.
  45. ↑ Lundmark K, Westermark GT, Olsen A, Westermark P (2005). "Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism". Proc Natl Acad Sci U S A. 102 (17): 6098–6102. PMC 1087940 Freely accessible. PMID 15829582. doi:10.1073/pnas.0501814102.
  46. ↑ Fu X, Korenaga T, Fu L, et al. (2004). "Induction of AApoAII amyloidosis by various heterogeneous amyloid fibrils". FEBS Lett. 563 (1–3): 179–184. PMID 15063745. doi:10.1016/S0014-5793(04)00295-9.
  47. ↑ Bolmont T, Clavaguera F, Meyer-Luehmann M, et al. (2007). "Induction of Tau Pathology by Intracerebral Infusion of Amyloid-β-Containing Brain Extract and by Amyloid-β Deposition in APP × Tau Transgenic Mice". Am J Pathol. 171 (6): 2012–2020. PMC 2111123 Freely accessible. PMID 18055549. doi:10.2353/ajpath.2007.070403.
  48. ↑ Morales R, et al. (2010). "Molecular Cross-talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases". J Neurosci. 30 (13): 4528–4535. PMC 2859074 Freely accessible. PMID 20357103. doi:10.1523/JNEUROSCI.5924-09.2010.
  49. 1 2 3 4 Revesz, Tamas; Ghiso, Jorge; Lashley, Tammaryn; Plant, Gordon; Rostagno, Agueda; Frangione, Blas; Holton, Janice L. (2003). "Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view". Journal of Neuropathology and Experimental Neurology. 62 (9): 885–898. ISSN 0022-3069.
  50. ↑ Guo L, et al. (2007). "Targeting amyloid-β in glaucoma treatment". Proc Natl Acad Sci U S A. 104 (33): 13444–13449. PMC 1940230 Freely accessible. PMID 17684098. doi:10.1073/pnas.0703707104.
  51. ↑ Prusiner, SB (2004). Prion Biology and Diseases (2 ed.). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN 0-87969-693-1.
  52. ↑ Goedert, Michel; Spillantini, Maria Grazia; Del Tredici, Kelly; Braak, Heiko (27 November 2012). "100 years of Lewy pathology". Nature Reviews Neurology. 9 (1): 13–24. doi:10.1038/nrneurol.2012.242.
  53. ↑ Clavaguera, Florence; Hench, Jürgen; Goedert, Michel; Tolnay, Markus (February 2015). "Invited review: Prion-like transmission and spreading of tau pathology". Neuropathology and Applied Neurobiology. 41 (1): 47–58. doi:10.1111/nan.12197.
  54. 1 2 Mann, David M.A.; Snowden, Julie S. (March 2017). "Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype". Brain Pathology. doi:10.1111/bpa.12486.
  55. ↑ Grad, Leslie I.; Fernando, Sarah M.; Cashman, Neil R. (May 2015). "From molecule to molecule and cell to cell: Prion-like mechanisms in amyotrophic lateral sclerosis". Neurobiology of Disease. 77: 257–265. doi:10.1016/j.nbd.2015.02.009.
  56. ↑ Ludolph, Albert C.; Brettschneider, Johannes; Weishaupt, Jochen H. (October 2012). "Amyotrophic lateral sclerosis". Current Opinion in Neurology. 25 (5): 530–535. doi:10.1097/WCO.0b013e328356d328.
  57. ↑ Orr, Harry T.; Zoghbi, Huda Y. (July 2007). "Trinucleotide Repeat Disorders". Annual Review of Neuroscience. 30 (1): 575–621. doi:10.1146/annurev.neuro.29.051605.113042.
  58. ↑ Almeida, Bruno; Fernandes, Sara; Abreu, Isabel A.; Macedo-Ribeiro, Sandra (2013). "Trinucleotide Repeats: A Structural Perspective". Frontiers in Neurology. 4. doi:10.3389/fneur.2013.00076.
  59. ↑ Spinner NB (2000). "CADASIL: Notch signaling defect or protein accumulation problem?". J Clin Invest. 105 (5): 561–562. PMC 292459 Freely accessible. PMID 10712425. doi:10.1172/JCI9511.
  60. ↑ Quinlan RA, Brenner M, Goldman JE, Messing A (2007). "GFAP and its role in Alexander Disease". Exp Cell Res. 313 (10): 2077–2087. PMC 2702672 Freely accessible. PMID 17498694. doi:10.1016/j.yexcr.2007.04.004.
  61. ↑ Ito D, Suzuki N (2009). "Seipinopathy: A novel endoplasmic reticulum stress-associated disease". Brain. 132 (Pt 1): 8–15. PMID 18790819. doi:10.1093/brain/awn216.
  62. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Sipe, Jean D.; Benson, Merrill D.; Buxbaum, Joel N.; Ikeda, Shu-ichi; Merlini, Giampaolo; Saraiva, Maria J. M.; Westermark, Per (24 November 2016). "Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines". Amyloid. 23 (4): 209–213. doi:10.1080/13506129.2016.1257986.
  63. ↑ Lomas, David A.; Carrell, Robin W. (October 2002). "Serpinopathies and the conformational dementias". Nature Reviews Genetics. 3 (10): 759–768. doi:10.1038/nrg907.
  64. ↑ Mukherjee, Abhisek; Soto, Claudio (3 February 2017). "Prion-Like Protein Aggregates and Type 2 Diabetes". Cold Spring Harbor Perspectives in Medicine: a024315. doi:10.1101/cshperspect.a024315.
  65. ↑ Askanas, V.; Engel, W. K. (16 December 2005). "Inclusion-body myositis: A myodegenerative conformational disorder associated with A , protein misfolding, and proteasome inhibition". Neurology. 66 (1, Supplement 1): S39–S48. doi:10.1212/01.wnl.0000192128.13875.1e.
  66. ↑ Ecroyd, H.; Carver, John A. (22 September 2008). "Crystallin proteins and amyloid fibrils". Cellular and Molecular Life Sciences. 66 (1): 62–81. doi:10.1007/s00018-008-8327-4.
  67. ↑ Surguchev A, Surguchov A (2010). "Conformational diseases: Looking into the eyes". Brain Res Bull. 81 (1): 12–24. PMID 19808079. doi:10.1016/j.brainresbull.2009.09.015.
  68. ↑ Huilgol, S. C.; Ramnarain, N.; Carrington, P.; Leigh, I. M.; Black, M. M. (1 May 1998). "Cytokeratins in primary cutaneous amyloidosis". The Australasian Journal of Dermatology. 39 (2): 81–85. ISSN 0004-8380.
  69. ↑ Janig, Elke; Stumptner, Cornelia; Fuchsbichler, Andrea; Denk, Helmut; Zatloukal, Kurt (March 2005). "Interaction of stress proteins with misfolded keratins". European Journal of Cell Biology. 84 (2-3): 329–339. doi:10.1016/j.ejcb.2004.12.018.
  70. ↑ D’Souza, Anita; Theis, Jason D.; Vrana, Julie A.; Dogan, Ahmet (2014). "Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration". Amyloid. 21 (2): 71–75. doi:10.3109/13506129.2013.876984.
  71. ↑ Meng, Xin; Clews, Jack; Kargas, Vasileios; Wang, Xiaomeng; Ford, Robert C. (12 October 2016). "The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability". Cellular and Molecular Life Sciences. 74 (1): 23–38. doi:10.1007/s00018-016-2386-8.
  72. ↑ Stuart MJ, Nagel RL (2004). "Sickle cell disease". Lancet. 364 (9442): 1343–1360. PMID 15474138. doi:10.1016/S0140-6736(04)17192-4.
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