The cellular prion protein and its derived fragments in human prion diseases and their role as potential biomarkers

References

• Soto C, Satani N. The intricate mechanisms of neurodegeneration in prion diseases. Trends Mol Med. 2011 Jan;17(1):14–24.
   PubMed Web of Science ®Google Scholar
• Appleby BS. Psychotropic medications and the treatment of human prion diseases. CNS Neurol Disord Drug Targets. 2009 Nov;8(5):353–362.
   PubMed Web of Science ®Google Scholar
• Prusiner SB. The prion diseases. Brain Pathol. 1998 Jul;8(3):499–513.
   PubMed Web of Science ®Google Scholar
• Aguzzi A, Heikenwalder M. Pathogenesis of prion diseases: current status and future outlook. Nat Rev Microbiol. 2006 Oct;4(10):765–775.
   PubMed Web of Science ®Google Scholar
• Wadsworth JD, Collinge J. Molecular pathology of human prion disease. Acta Neuropathol. 2011 Jan;121(1):69–77.
   PubMed Web of Science ®Google Scholar
• Gambetti P, Kong Q, Zou W, et al. Sporadic and familial CJD: classification and characterisation. Br Med Bull. 2003;66:213–239.
   PubMed Web of Science ®Google Scholar
• Pedersen JT, Heegaard NH. Analysis of protein aggregation in neurodegenerative disease. Anal Chem. 2013 May 7;85(9):4215–4227.
   PubMed Web of Science ®Google Scholar
• Kovac V, Curin Serbec V. Prion proteins without the glycophosphatidylinositol anchor: potential biomarkers in neurodegenerative diseases. Biomark Insights. 2018;13:1177271918756648.
   Web of Science ®Google Scholar
• Choi JK, Cali I, Surewicz K, et al. Amyloid fibrils from the N-terminal prion protein fragment are infectious. Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13851–13856.
   PubMed Web of Science ®Google Scholar
• Flores-Rodriguez P, Ontiveros-Torres MA, Cardenas-Aguayo MC, et al. The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer’s disease. Front Neurosci. 2015;9:33.
   PubMed Web of Science ®Google Scholar
• van der Wateren IM, Knowles TPJ, Buell AK, et al. C-terminal truncation of alpha-synuclein promotes amyloid fibril amplification at physiological pH. Chem Sci. 2018 Jul 7;9(25):5506–5516.
   PubMed Web of Science ®Google Scholar
• Ozcelik S, Sprenger F, Skachokova Z, et al. Co-expression of truncated and full-length tau induces severe neurotoxicity. Mol Psychiatry. 2016 Dec;21(12):1790–1798.
   PubMed Web of Science ®Google Scholar
• Terada M, Suzuki G, Nonaka T, et al. The effect of truncation on prion-like properties of alpha-synuclein. J Biol Chem. 2018 Sep 7;293(36):13910–13920.
   PubMed Web of Science ®Google Scholar
• Fortelny N, Pavlidis P, Overall CM. The path of no return–truncated protein N-termini and current ignorance of their genesis. Proteomics. 2015 Jul;15(14):2547–2552.
   PubMed Web of Science ®Google Scholar
• Demir F, Niedermaier S, Kizhakkedathu JN, et al. Profiling of protein N-Termini and their modifications in complex samples. Methods Mol Biol. 2017;1574:35–50.
   PubMedGoogle Scholar
• Bartha I, Rausell A, McLaren PJ, et al. The characteristics of heterozygous protein truncating variants in the human genome. PLoS Comput Biol. 2015 Dec;11(12):e1004647.
   PubMed Web of Science ®Google Scholar
• DeBoever C, Tanigawa Y, Lindholm ME, et al. Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study. Nat Commun. 2018 Apr 24;9(1):1612.
   PubMed Web of Science ®Google Scholar
• Rivas MA, Graham D, Sulem P, et al. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis. Nat Commun. 2016 Aug 9;7:12342.
   PubMed Web of Science ®Google Scholar
• Abul-Husn NS, Cheng X, Li AH, et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018 Mar 22;378(12):1096–1106.
   PubMed Web of Science ®Google Scholar
• Jahn TR, Radford SE. Folding versus aggregation: polypeptide conformations on competing pathways. Arch Biochem Biophys. 2008 Jan 1;469(1):100–117.
   PubMed Web of Science ®Google Scholar
• Chiti F, Dobson CM. Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade. Annu Rev Biochem. 2017 Jun;20(86):27–68.
   Web of Science ®Google Scholar
• Wang W, Nguyen LT, Burlak C, et al. Caspase-1 causes truncation and aggregation of the Parkinson’s disease-associated protein alpha-synuclein. Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9587–9592.
   PubMed Web of Science ®Google Scholar
• Dunys J, Valverde A, Are N- CF. C-terminally truncated Abeta species key pathological triggers in Alzheimer’s disease? J Biol Chem. 2018 Oct 5;293(40):15419–15428.
   PubMed Web of Science ®Google Scholar
• Villar-Pique A, Schmitz M, Candelise N, et al. Molecular and clinical aspects of protein aggregation assays in neurodegenerative diseases. Mol Neurobiol. 2018: Epub ahead of print
   Web of Science ®Google Scholar
• Kovac V, Zupancic B, Ilc G, et al. Truncated prion protein PrP226* - a structural view on its role in amyloid disease. Biochem Biophys Res Commun. 2017 Feb 26;484(1):45–50.
   PubMed Web of Science ®Google Scholar
• Tagliavini F, Prelli F, Porro M, et al. A soluble form of prion protein in human cerebrospinal fluid: implications for prion-related encephalopathies. Biochem Biophys Res Commun. 1992 May 15;184(3):1398–1404.
   PubMed Web of Science ®Google Scholar
• Wong BS, Green AJ, Li R, et al. Absence of protease-resistant prion protein in the cerebrospinal fluid of Creutzfeldt-Jakob disease. J Pathol. 2001 May;194(1):9–14.
   PubMed Web of Science ®Google Scholar
• Meyne F, Gloeckner SF, Ciesielczyk B, et al. Total prion protein levels in the cerebrospinal fluid are reduced in patients with various neurological disorders. J Alzheimers Dis. 2009;17(4):863–873.
   PubMed Web of Science ®Google Scholar
• Torres M, Cartier L, Matamala JM, et al. Altered Prion protein expression pattern in CSF as a biomarker for Creutzfeldt-Jakob disease. PLoS One. 2012;7(4):e36159.
   PubMed Web of Science ®Google Scholar
• Stahl N, Borchelt DR, Hsiao K, et al. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell. 1987 Oct 23;51(2):229–240.
   PubMed Web of Science ®Google Scholar
• Prado MA, Alves-Silva J, Magalhaes AC, et al. PrPC on the road: trafficking of the cellular prion protein. J Neurochem. 2004 Feb;88(4):769–781.
   PubMed Web of Science ®Google Scholar
• De Mario A, Peggion C, Massimino ML, et al. The prion protein regulates glutamate-mediated Ca(2+) entry and mitochondrial Ca(2+) accumulation in neurons. J Cell Sci. 2017 Aug 15;130(16):2736–2746.
   PubMed Web of Science ®Google Scholar
• Lauren J, Gimbel DA, Nygaard HB, et al. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009 Feb 26;457(7233):1128–1132.
   Google Scholar
• Schmitz M, Hermann P, Oikonomou P, et al. Cytokine profiles and the role of cellular prion protein in patients with vascular dementia and vascular encephalopathy. Neurobiol Aging. 2015 Sep;36(9):2597–2606.
   PubMed Web of Science ®Google Scholar
• Castle AR, Gill AC. Physiological functions of the cellular prion protein. Front Mol Biosci. 2017;4:19.
   PubMed Web of Science ®Google Scholar
• Wulf MA, Senatore A, Aguzzi A. The biological function of the cellular prion protein: an update. BMC Biol. 2017 May 2;15(1):34.
   PubMed Web of Science ®Google Scholar
• Steele AD, Emsley JG, Ozdinler PH, et al. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3416–3421.
   PubMed Web of Science ®Google Scholar
• Ramljak S, Schmitz M, Zafar S, et al. Cellular prion protein directly interacts with and enhances lactate dehydrogenase expression under hypoxic conditions. Exp Neurol. 2015;271:155–167.
   PubMed Web of Science ®Google Scholar
• Ferreira DG, Temido-Ferreira M, Vicente Miranda H, et al. Alpha-synuclein interacts with PrP(C) to induce cognitive impairment through mGluR5 and NMDAR2B. Nat Neurosci. 2017 Nov;20(11):1569–1579.
   PubMed Web of Science ®Google Scholar
• Linsenmeier L, Mohammadi B, Wetzel S, et al. Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein. Mol Neurodegener. 2018;13(1):18.
   PubMed Web of Science ®Google Scholar
• Linsenmeier L, Altmeppen HC, Wetzel S, et al. Diverse functions of the prion protein - does proteolytic processing hold the key? Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11Pt B):2128–2137.
   PubMed Web of Science ®Google Scholar
• Altmeppen HC, Prox J, Krasemann S, et al. The sheddase ADAM10 is a potent modulator of prion disease. Elife. 2015 Feb 5;(4):1–50.
   Google Scholar
• Beringue V, Mallinson G, Kaisar M, et al. Regional heterogeneity of cellular prion protein isoforms in the mouse brain. Brain. 2003 Sep;126(Pt 9):2065–2073.
   PubMed Web of Science ®Google Scholar
• Gasperini L, Legname G. Prion protein and aging. Front Cell Dev Biol. 2014;2:44
   PubMed Web of Science ®Google Scholar
• Zanusso G, Farinazzo A, Prelli F, et al. Identification of distinct N-terminal truncated forms of prion protein in different Creutzfeldt-Jakob disease subtypes. J Biol Chem. 2004 Sep 10;279(37):38936–38942.
   PubMed Web of Science ®Google Scholar
• Schmitz M, Lullmann K, Zafar S, et al. Association of prion protein genotype and scrapie prion protein type with cellular prion protein charge isoform profiles in cerebrospinal fluid of humans with sporadic or familial prion diseases. Neurobiol Aging. 2014 May;35(5):1177–1188.
   PubMed Web of Science ®Google Scholar
• Pan T, Li R, Wong BS, et al. Heterogeneity of normal prion protein in two- dimensional immunoblot: presence of various glycosylated and truncated forms. J Neurochem. 2002 Jun;81(5):1092–1101.
   PubMed Web of Science ®Google Scholar
• Pan T, Wong BS, Liu T, et al. Cell-surface prion protein interacts with glycosaminoglycans. Biochem J. 2002 Nov 15;368(Pt 1):81–90.
   PubMed Web of Science ®Google Scholar
• Pan T, Colucci M, Wong BS, et al. Novel differences between two human prion strains revealed by two-dimensional gel electrophoresis. J Biol Chem. 2001 Oct 5;276(40):37284–37288.
   PubMed Web of Science ®Google Scholar
• Laffont-Proust I, Hassig R, Haik S, et al. Truncated PrP(c) in mammalian brain: interspecies variation and location in membrane rafts. Biol Chem. 2006 Mar;387(3):297–300.
   PubMed Web of Science ®Google Scholar
• Jimenez-Huete A, Lievens PM, Vidal R, et al. Endogenous proteolytic cleavage of normal and disease-associated isoforms of the human prion protein in neural and non-neural tissues. Am J Pathol. 1998 Nov;153(5):1561–1572.
   PubMed Web of Science ®Google Scholar
• Haigh CL, Collins SJ. Endoproteolytic cleavage as a molecular switch regulating and diversifying prion protein function. Neural Regen Res. 2016 Feb;11(2):238–239.
   PubMed Web of Science ®Google Scholar
• Caughey B, Race RE, Ernst D, et al. Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells. J Virol. 1989 Jan;63(1):175–181.
   PubMed Web of Science ®Google Scholar
• Shyng SL, Huber MT, Harris DA. A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. J Biol Chem. 1993 Jul 25;268(21):15922–15928.
   PubMed Web of Science ®Google Scholar
• Chen SG, Teplow DB, Parchi P, et al. Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem. 1995 Aug 11;270(32):19173–19180.
   PubMed Web of Science ®Google Scholar
• Lewis V, Johanssen VA, Crouch PJ, et al. Prion protein “gamma-cleavage”: characterizing a novel endoproteolytic processing event. Cell Mol Life Sci. 2016 Feb;73(3):667–683.
   PubMed Web of Science ®Google Scholar
• Lewis V, Hill AF, Haigh CL, et al. Increased proportions of C1 truncated prion protein protect against cellular M1000 prion infection. J Neuropathol Exp Neurol. 2009 Oct;68(10):1125–1135.
   PubMed Web of Science ®Google Scholar
• Altmeppen HC, Puig B, Dohler F, et al. Proteolytic processing of the prion protein in health and disease. Am J Neurodegener Dis. 2012;1(1):15–31.
   PubMedGoogle Scholar
• McDonald AJ, Millhauser GL. PrP overdrive: does inhibition of alpha-cleavage contribute to PrP(C) toxicity and prion disease? Prion. 2014 Mar-Apr;8(2):183–191.
   PubMed Web of Science ®Google Scholar
• Mange A, Beranger F, Peoc’h K, et al. Alpha- and beta- cleavages of the amino-terminus of the cellular prion protein. Biol Cell. 2004 Mar;96(2):125–132.
   PubMed Web of Science ®Google Scholar
• Westergard L, Turnbaugh JA, Harris DA. A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation. J Biol Chem. 2011 Dec 23;286(51):44234–44242.
   PubMed Web of Science ®Google Scholar
• Altmeppen HC, Prox J, Puig B, et al. Roles of endoproteolytic alpha-cleavage and shedding of the prion protein in neurodegeneration. Febs J. 2013 Sep;280(18):4338–4347.
   PubMed Web of Science ®Google Scholar
• Sanchez-Lopez C, Fernandez CO, Quintanar L. Neuroprotective alpha-cleavage of the human prion protein significantly impacts Cu(ii) coordination at its His111 site. Dalton Trans. 2018 Jul 17;47(28):9274–9282.
   PubMed Web of Science ®Google Scholar
• Liang J, Kong Q. Alpha-Cleavage of cellular prion protein. Prion. 2012 Nov-Dec;6(5):453–460.
   PubMed Web of Science ®Google Scholar
• Caughey B, Raymond GJ, Ernst D, et al. N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol. 1991 Dec;65(12):6597–6603.
   PubMed Web of Science ®Google Scholar
• Watt NT, Taylor DR, Gillott A, et al. Reactive oxygen species-mediated beta-cleavage of the prion protein in the cellular response to oxidative stress. J Biol Chem. 2005 Oct 28;280(43):35914–35921.
   PubMed Web of Science ®Google Scholar
• Perini F, Vidal R, Ghetti B, et al. PrP27-30 is a normal soluble prion protein fragment released by human platelets. Biochem Biophys Res Commun. 1996 Jun 25;223(3):572–577.
   PubMed Web of Science ®Google Scholar
• MacGregor I, Hope J, Barnard G, et al. Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components. Vox Sang. 1999;77(2):88–96.
   PubMed Web of Science ®Google Scholar
• Glatzel M, Linsenmeier L, Dohler F, et al. Shedding light on prion disease. Prion. 2015;9(4):244–256.
   PubMed Web of Science ®Google Scholar
• Altmeppen HC, Prox J, Puig B, et al. Lack of a-disintegrin-and-metalloproteinase ADAM10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo. Mol Neurodegener. 2011 May 27;6:36.
   PubMed Web of Science ®Google Scholar
• Taylor DR, Parkin ET, Cocklin SL, et al. Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein. J Biol Chem. 2009 Aug 21;284(34):22590–22600.
   PubMed Web of Science ®Google Scholar
• Tucher J, Linke D, Koudelka T, et al. LC-MS based cleavage site profiling of the proteases ADAM10 and ADAM17 using proteome-derived peptide libraries. J Proteome Res. 2014 Apr 4;13(4):2205–2214.
   PubMed Web of Science ®Google Scholar
• Schmitz M, Schlomm M, Hasan B, et al. Codon 129 polymorphism and the E200K mutation do not affect the cellular prion protein isoform composition in the cerebrospinal fluid from patients with Creutzfeldt-Jakob disease. Eur J Neurosci. 2010 Jun;31(11):2024–2031.
   PubMed Web of Science ®Google Scholar
• Castagna A, Campostrini N, Farinazzo A, et al. Comparative two-dimensional mapping of prion protein isoforms in human cerebrospinal fluid and central nervous system. Electrophoresis. 2002 Jan;23(2):339–346.
   PubMed Web of Science ®Google Scholar
• Schulz-Schaeffer WJ, Tschoke S, Kranefuss N, et al. The paraffin-embedded tissue blot detects PrP(Sc) early in the incubation time in prion diseases. Am J Pathol. 2000 Jan;156(1):51–56.
   PubMed Web of Science ®Google Scholar
• Büeler H, Raeber A, Sailer A, et al. High prion and PrPSc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted PrP gene. Mol Med. 1994 Nov;1(1):19–30.
   PubMed Web of Science ®Google Scholar
• Moreno JA, Radford H, Peretti D, et al. Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration. Nature. 2012 May 6;485(7399):507–511.
   PubMed Web of Science ®Google Scholar
• Safar JG, DeArmond SJ, Kociuba K, et al. Prion clearance in bigenic mice. J Gen Virol. 2005 Oct;86(Pt 10):2913–2923.
   PubMed Web of Science ®Google Scholar
• Mays CE, Kim C, Haldiman T, et al. Prion disease tempo determined by host-dependent substrate reduction. J Clin Invest. 2014 Feb;124(2):847–858.
   PubMed Web of Science ®Google Scholar
• Jansen C, Parchi P, Capellari S, et al. Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP. Acta Neuropathol. 2010 Feb;119(2):189–197.
   PubMed Web of Science ®Google Scholar
• Dvorakova E, Vranac T, Janouskova O, et al. Detection of the GPI-anchorless prion protein fragment PrP226* in human brain. BMC Neurol. 2013 Sep 25;13:126.
   PubMed Web of Science ®Google Scholar
• Lukan A, Cernilec M, Vranac T, et al. Regional distribution of anchorless prion protein, PrP226*, in the human brain. Prion. 2014 Mar-Apr;8(2):203–209.
   PubMed Web of Science ®Google Scholar
• Curin Serbec V, Bresjanac M, Popovic M, et al. Monoclonal antibody against a peptide of human prion protein discriminates between Creutzfeldt-Jacob’s disease-affected and normal brain tissue. J Biol Chem. 2004 Jan 30;279(5):3694–3698.
   PubMed Web of Science ®Google Scholar
• Minikel EV, Kuhn E, Cocco A, et al. Domain-specific quantification of prion protein in cerebrospinal fluid by targeted mass spectrometry. bioRxiv. 2019 Apr 16;116(16):7793–7798.
   Google Scholar
• Geschwind MD. Prion Diseases. Continuum (Minneap Minn). 2015 Dec;21(6 Neuroinfectious Disease):1612–1638.
   PubMedGoogle Scholar
• Imran M, Mahmood S. An overview of human prion diseases. Virol J. 2011 Dec;24(8):559.
   Web of Science ®Google Scholar
• Sikorska B, Liberski PP. Human prion diseases: from Kuru to variant Creutzfeldt-Jakob disease. Subcell Biochem. 2012;65:457–496.
   PubMedGoogle Scholar
• Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain. 2009 Oct;132(Pt 10):2659–2668.
   PubMed Web of Science ®Google Scholar
• Atarashi R, Satoh K, Sano K, et al. Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. Nat Med. 2011 Feb;17(2):175–178.
   PubMed Web of Science ®Google Scholar
• McGuire LI, Peden AH, Orru CD, et al. Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 2012 Aug;72(2):278–285.
   PubMed Web of Science ®Google Scholar
• Cramm M, Schmitz M, Karch A, et al. Stability and reproducibility underscore utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease. Mol Neurobiol. 2016 Apr;53(3):1896–1904.
   PubMed Web of Science ®Google Scholar
• Schmitz M, Cramm M, Llorens F, et al. The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases. Nat Protoc. 2016 Nov;11(11):2233–2242.
   PubMed Web of Science ®Google Scholar
• Schmitz M, Candelise N, Llorens F, et al. Amplification and detection of minuscule amounts of misfolded prion protein by using the real-time quaking-induced conversion. Methods Mol Biol. 2018;1779:257–263.
   PubMedGoogle Scholar
• Llorens F, Kruse N, Karch A, et al. Validation of alpha-synuclein as a CSF biomarker for Sporadic Creutzfeldt-Jakob disease. Mol Neurobiol. 2018 Mar;55(3):2249–2257.
   PubMed Web of Science ®Google Scholar
• Sanchez-Juan P, Green A, Ladogana A, et al. CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology. 2006 Aug 22;67(4):637–643.
   PubMed Web of Science ®Google Scholar
• Llorens F, Schmitz M, Karch A, et al. Comparative analysis of cerebrospinal fluid biomarkers in the differential diagnosis of neurodegenerative dementia. Alzheimers Dement. 2016 May;12(5):577–589.
   PubMed Web of Science ®Google Scholar
• Collins SJ, Sanchez-Juan P, Masters CL, et al. Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease. Brain. 2006 Sep;129(Pt 9):2278–2287.
   PubMed Web of Science ®Google Scholar
• Llorens F, Schmitz M, Ferrer I, et al. CSF biomarkers in neurodegenerative and vascular dementias. Prog Neurobiol. 2016 Mar-May;36–53:138–140.
   Google Scholar
• Castellani RJ, Colucci M, Xie Z, et al. Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt-Jakob disease. Neurology. 2004 Aug 10;63(3):436–442.
   PubMed Web of Science ®Google Scholar
• Llorens F, Ansoleaga B, Garcia-Esparcia P, et al. PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2. Prion. 2013 Sep-Oct;7(5):383–393.
   PubMed Web of Science ®Google Scholar
• Llorens F, Lopez-Gonzalez I, Thune K, et al. Subtype and regional-specific neuroinflammation in sporadic Creutzfeldt-Jakob disease. Front Aging Neurosci. 2014;6:198.
   PubMed Web of Science ®Google Scholar
• Abu Rumeileh S, Lattanzio F, Stanzani Maserati M, et al. Diagnostic accuracy of a combined analysis of cerebrospinal fluid t-PrP, t-tau, p-tau, and Abeta42 in the differential Diagnosis of Creutzfeldt-Jakob Disease from Alzheimer’s Disease with emphasis on atypical disease variants. J Alzheimers Dis. 2017;55(4):1471–1480.
   PubMed Web of Science ®Google Scholar
• Dorey A, Tholance Y, Vighetto A, et al. Association of cerebrospinal fluid prion protein levels and the distinction between Alzheimer disease and Creutzfeldt-Jakob disease. JAMA Neurol. 2015 Mar;72(3):267–275.
   PubMed Web of Science ®Google Scholar
• Villar-Pique A, Schmitz M, Lachmann I, et al. Cerebrospinal fluid total prion protein in the spectrum of prion diseases. Mol Neurobiol. 2019 Apr;56(4):2811–2821.
   PubMed Web of Science ®Google Scholar
• Schmitz M, Cramm M, Llorens F, et al. Application of an in vitro-amplification assay as a novel pre-screening test for compounds inhibiting the aggregation of prion protein scrapie. Sci Rep. 2016 Jul;07(6):28711.
   Web of Science ®Google Scholar
• Llorens F, Schmitz M, Zerr I. Progress in CSF biomarker discovery in sCJD. Oncotarget. 2017 Jan 24;8(4):5666–5667.
   PubMedGoogle Scholar
• Gaetani L, Blennow K, Calabresi P, et al. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):870–881.
   PubMed Web of Science ®Google Scholar
• Baldacci F, Lista S, Palermo G, et al. The neuroinflammatory biomarker YKL-40 for neurodegenerative diseases: advances in development. Expert Rev Proteomics. 2019 Jul;16(7):593–600.
   PubMed Web of Science ®Google Scholar
• Vallabh SM, Nobuhara CK, Llorens F, et al. Prion protein quantification in human cerebrospinal fluid as a tool for prion disease drug development. Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7793–7798.
   PubMed Web of Science ®Google Scholar
• Ghetti B, Piccardo P, Spillantini MG, et al. Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):744–748.
   PubMed Web of Science ®Google Scholar
• Revesz T, Holton JL, Lashley T, et al. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009 Jul;118(1):115–130.
   PubMed Web of Science ®Google Scholar
• Notari S, Strammiello R, Capellari S, et al. Characterization of truncated forms of abnormal prion protein in Creutzfeldt-Jakob disease. J Biol Chem. 2008 Nov 07;283(45):30557–30565.
   PubMed Web of Science ®Google Scholar
• Zou WQ, Capellari S, Parchi P, et al. Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt-Jakob disease. J Biol Chem. 2003 Oct 17;278(42):40429–40436.
   PubMed Web of Science ®Google Scholar
• Honda H, Matsuzono K, Fushimi S, et al. C-Terminal-deleted prion protein fragment is a major accumulated component of systemic PrP deposits in hereditary prion disease with a 2-Bp (CT) deletion in PRNP Codon 178. J Neuropathol Exp Neurol. 2016Sep;15(75):1008–1019.
   Web of Science ®Google Scholar
• Kovac V, Hafner-Bratkovic I, Curin Serbec V. Anchorless forms of prion protein - impact of truncation on structure destabilization and prion protein conversion. Biochem Biophys Res Commun. 2016 Dec 2;481(1–2):1–6.
   PubMed Web of Science ®Google Scholar
• Parchi P, Chen SG, Brown P, et al. Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Straussler-Scheinker disease. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8322–8327.
   PubMed Web of Science ®Google Scholar
• Tagliavini F, Prelli F, Ghiso J, et al. Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. Embo J. 1991 Mar;10(3):513–519.
   PubMed Web of Science ®Google Scholar
• Meyer RK, McKinley MP, Bowman KA, et al. Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2310–2314.
   PubMed Web of Science ®Google Scholar
• Parchi P, Zou W, Wang W, et al. Genetic influence on the structural variations of the abnormal prion protein. Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10168–10172.
   PubMed Web of Science ®Google Scholar
• Parchi P, Capellari S, Chen SG, et al. Typing prion isoforms. Nature. 1997 Mar 20;386(6622):232–234.
   PubMed Web of Science ®Google Scholar
• Satoh K, Muramoto T, Tanaka T, et al. Association of an 11–12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases. J Gen Virol. 2003 Oct;84(Pt 10):2885–2893.
   PubMed Web of Science ®Google Scholar
• Kobayashi A, Parchi P, Yamada M, et al. Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology? J Virol. 2015 Apr;89(7):3939–3946.
   PubMed Web of Science ®Google Scholar
• Singh N, Gu Y, Bose S, et al. Processing and mis-processing of the prion protein: insights into the pathogenesis of familial prion disorders. In: D. Brown, editors. Neurodegeneration and Prion Disease. New York: Life Sciences, Springer; 2005. p. 299–318.
   Google Scholar
• Zhu JB, Tan CC, Tan L, et al. State of play in Alzheimer’s disease genetics. J Alzheimers Dis. 2017;58(3):631–659.
   PubMed Web of Science ®Google Scholar
• Agbas A. Trends of protein aggregation in neurodegenerative diseases. In: T. Heinbockel and A. B. Csoka, editors. Neurochemical Basis of Brain Function and Dysfunction. Kansas City: Department of Basic Sciences, Kansas City University of Medicine and Biosciences; 2018. p. 1–19. .
   Google Scholar
• Brower CS, Piatkov KI, Varshavsky A. Neurodegeneration-associated protein fragments as short-lived substrates of the N-end rule pathway. Mol Cell. 2013 Apr 25;50(2):161–171.
   PubMed Web of Science ®Google Scholar
• Skrabana R, Kovacech B, Filipcik P, et al. Neuronal expression of truncated tau efficiently promotes neurodegeneration in animal models: pitfalls of toxic oligomer analysis. J Alzheimers Dis. 2017;58(4):1017–1025.
   PubMed Web of Science ®Google Scholar
• Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006 Oct 6;314(5796):130–133.
   PubMed Web of Science ®Google Scholar
• Polyakova O, Dear D, Stern I, et al. Proteolysis of prion protein by cathepsin S generates a soluble beta-structured intermediate oligomeric form, with potential implications for neurotoxic mechanisms. Eur Biophys J. 2009 Feb;38(2):209–218.
   PubMed Web of Science ®Google Scholar
• Yadavalli R, Guttmann RP, Seward T, et al. Calpain-dependent endoproteolytic cleavage of PrPSc modulates scrapie prion propagation. J Biol Chem. 2004 May 21;279(21):21948–21956.
   PubMed Web of Science ®Google Scholar
• Wang X, Wang F, Sy MS, et al. Calpain and other cytosolic proteases can contribute to the degradation of retro-translocated prion protein in the cytosol. J Biol Chem. 2005 Jan 7;280(1):317–325.
   PubMed Web of Science ®Google Scholar
• Dimcheff DE, Portis JL, Caughey B. Prion proteins meet protein quality control. Trends Cell Biol. 2003 Jul;13(7):337–340.
   PubMed Web of Science ®Google Scholar
• Georgieva D, Koker M, Redecke L, et al. Oligomerization of the proteolytic products is an intrinsic property of prion proteins. Biochem Biophys Res Commun. 2004 Oct 29;323(4):1278–1286.
   PubMed Web of Science ®Google Scholar
• Llorens F, Thune K, Sikorska B, et al. Altered Ca(2+) homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease. Acta Neuropathol Commun. 2017 Apr 27;5(1):35.
   PubMed Web of Science ®Google Scholar
• Xiang W, Windl O, Wunsch G, et al. Identification of differentially expressed genes in scrapie-infected mouse brains by using global gene expression technology. J Virol. 2004 Oct;78(20):11051–11060.
   PubMed Web of Science ®Google Scholar
• Turk B, Turk D, Turk V. Lysosomal cysteine proteases: more than scavengers. Biochim Biophys Acta. 2000 Mar 7;1477(1–2):98–111.
   PubMed Web of Science ®Google Scholar
• Capellari S, Baiardi S, Rinaldi R, et al. Two novel PRNP truncating mutations broaden the spectrum of prion amyloidosis. Ann Clin Transl Neurol. 2018 Jun;5(6):777–783.
   PubMed Web of Science ®Google Scholar
• Gerstmann J, Sträussler E, Scheinker I. Über eine eigenartige hereditär-familiäre Erkrankung des Zentralnervensystems. Zugleich ein Beitrag zur Frage des vorzeitigen lokalen Alterns. 1936;154:736–762. Z ges Neurol Psychiat.
   Google Scholar
• Schmitz M, Dittmar K, Llorens F, et al. hereditary human prion diseases: an update. Mol Neurobiol. 2017 Aug;54(6):4138–4149.
   PubMed Web of Science ®Google Scholar
• Tagliavini F, Lievens PM, Tranchant C, et al. A 7-kDa prion protein (PrP) fragment, an integral component of the PrP region required for infectivity, is the major amyloid protein in Gerstmann-Straussler-Scheinker disease A117V. J Biol Chem. 2001 Feb 23;276(8):6009–6015.
   PubMed Web of Science ®Google Scholar
• Bugiani O, Giaccone G, Piccardo P, et al. Neuropathology of Gerstmann-Straussler-Scheinker disease. Microsc Res Tech. 2000 Jul 1;50(1):10–15.
   PubMed Web of Science ®Google Scholar
• Cracco L, Xiao X, Nemani SK, et al. Gerstmann-Straussler-Scheinker disease revisited: accumulation of covalently-linked multimers of internal prion protein fragments. Acta Neuropathol Commun. 2019 May 29;7(1):1.
   PubMed Web of Science ®Google Scholar
• Kovacs GG, Budka H. Molecular pathology of human prion diseases. Int J Mol Sci. 2009 Mar;10(3):976–999.
   PubMed Web of Science ®Google Scholar
• Llorens F, Barrio T, Correia A, et al. Cerebrospinal fluid prion disease biomarkers in pre-clinical and clinical naturally occurring scrapie. Mol Neurobiol. 2018 Nov;55(11):8586–8591.
   PubMed Web of Science ®Google Scholar
• Watts JC, Prusiner SB. Experimental models of inherited PrP prion diseases. Cold Spring Harb Perspect Med. 2017 Nov 1;7(11).
   PubMed Web of Science ®Google Scholar
• Mercer RCC, Daude N, Dorosh L, et al. A novel Gerstmann-Straussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles. PLoS Pathog. 2018 Jan;14(1):e1006826.
   PubMed Web of Science ®Google Scholar