Misfolding of the prion protein: linking biophysical and biological approaches

Noinville, Sylvie; Chich, Jean-François; Rézaei, Human

doi:10.1051/vetres:2008025

Cited by 18 publications

(13 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They are based on the properties of recombinant PrP to polymerize into amyloid fibrils either spontaneously or upon addition of a small amount of pre-formed fibrils. Such a seeding effect is a feature of the nucleation-dependant polymerization process (for reviews see [14,139,187]). Surewicz et al elegantly modeled 'prion strain' diversity in a simple system consisting of seeded fibrilization of soluble monomeric prion protein variants (PrP23-144).…”

Section: Studies With Recombinant Prpmentioning

confidence: 99%

Prion agent diversity and species barrier

2008

View full text Add to dashboard Cite

-Mammalian prions are the infectious agents responsible for transmissible spongiform encephalopathies (TSE), a group of fatal, neurodegenerative diseases, affecting both domestic animals and humans. The most widely accepted view to date is that these agents lack a nucleic acid genome and consist primarily of PrP Sc , a misfolded, aggregated form of the host-encoded cellular prion protein (PrP C ) that propagates by autocatalytic conversion and accumulates mainly in the brain. The BSE epizooty, allied with the emergence of its human counterpart, variant CJD, has focused much attention on two characteristics that prions share with conventional infectious agents. First, the existence of multiple prion strains that impose, after inoculation in the same host, specific and stable phenotypic traits such as incubation period, molecular pattern of PrP Sc and neuropathology. Prion strains are thought to be enciphered within distinct PrP Sc conformers. Second, a transmission barrier exists that restricts the propagation of prions between different species. Here we discuss the possible situations resulting from the confrontation between species barrier and prion strain diversity, the molecular mechanisms involved and the potential of interspecies transmission of animal prions, including recently discovered forms of TSE in ruminants.prion / strain / misfolding / species barrier / PrP Table of Mammalian prion diseases or transmissible spongiform encephalopathies (TSE) form a group of related, invariably fatal neurodegenerative disorders of both animals and humans. The brain pathology consists of spongiosis, astrocytosis, neuronal loss and neural tissue from affected individuals contains an infectious agent, the prion, setting these diseases apart from other neurodegenerative diseases. Prion replication is thought to involve in essence the self-perpetuating conversion of the host-encoded cellular prion protein (PrP C ) into a misfolded form (PrP Sc ) that tends to aggregate and may be neurotoxic (for reviews [1,157]). Prion replication may also occur in lymphoid tissues but is there poorly if not pathogenic (for review [126], [133]). PrP C is a protein with two variably occupied glycosylation sites. It is attached at the outer of the plasma membrane by a glycosylphosphatidylinositol anchor. Its secondary structure is rich in alpha-helix and the protein is likely to be in a monomeric state in mild detergents. While its precise physiological function has not been assigned, PrP C is essential for prion replication and neurotoxicity to occur [57,129]. Upon infection, PrP C is refolded -without apparent post-translational modification -into beta-sheet -rich PrP Sc , initially in the presence of exogenous PrP Sc and then by an autocatalytic process. It leads to the formation of aggregates, sometimes of amyloid type, that can be differentiated from PrP C because of their partial resistance to protease digestion and of their insolubility into non-denaturing detergents [153]. Proteinase K, the most commonly used protease, di...

show abstract

Section: Studies With Recombinant Prpmentioning

confidence: 99%

Prion agent diversity and species barrier

2008

View full text Add to dashboard Cite

show abstract

“…Indeed, physiological PrP C trafficking results in its localization on the plasma membrane, in subcellular compartments and vehicles, 38 and enables its co-localization with PrP SC on the plasma membrane as well as in endo-cellular compartments with low pH, 39 where conversion takes place. 37,40 We ensured physiological cell trafficking of the studied protein variants and their subsequent binding to the plasma membrane, by expressing murine-caprine chimeras consisting of the mature caprine PrP sequence, flanked by murine PrP regulatory elements, to enable Endoplasmatic Reticulum lumen targeting and GPI-anchor addition. Efficient conversion depends on the compatibility of the interacting PrP isoforms and is associated with both their primary sequence and structural similarity.…”

Section: Discussionmentioning

confidence: 99%

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells

Kanata

Arsenakis

Sklaviadis

2016

Prion

View full text Add to dashboard Cite

“…Prion hipotezi ya da "protein-only" hipotezi viruslar ya da nukleik asitler yerine proteinlerin infeksiyöz olduğunu ve kalıtsal bilgi taşıyabileceğini ileri sür-mektedir [112]. Bir proteinin kendini çeşitli şekillerde çoğaltabilen konformasyonlara yanlış olarak katlanmasının maya, mantar ve son yıllarda insanlarda prion kalıtımının orijini olabileceği düşünülmektedir [113,114].…”

Section: Prion Hipoteziunclassified

Prion Proteinlerinin Biyolojisi / Biology of Prion Proteins

Balcan¹

2017

Celal Bayar Üniversitesi Fen Bilimleri Dergisi

View full text Add to dashboard Cite

ÖzetAlzheimer, Parkinson, Huntington ve prion hastalıkları gibi nörodejeneratif bozukluklarda ortak özellik, yanlış katlanma gösteren spesifik proteinlerin kümelenmesi ve geniş amiloid fibril ya da plakların oluşu-mudur. Son bulgular küçük soluble oligomerlerin nöronal yetersizlikten öncelikli olarak sorumlu olduğunu göstermiştir. Glikozilfosfatidilinozitol (GPI) çapalı hücresel bir glikoprotein olan prion proteini insan ve hayvanlarda prion hastalıkları olarak bilinen transmissible spongiform ensefalopatilerin (TSE) patogenezinde önemli bir rol oynamaktadır. Prion hastalıklarında bu proteinin normal hücresel formu (PrP C ) hastalık etkeni izoforma (PrP Sc ) dönüşebilir. Prion proteinlerinin bu yapısal dönüşüm sırasında kullandığı moleküler stratejiler henüz tam olarak anlaşılamamış olmasına karşın bu proteinin nörodejeneratif hastalıkların etyolojisinde ve patolojisinde merkezi bir rol oynadığı ve prion proteinlerini kodlayan genlerin (Prnp) mutasyonları ve polimorfizmlerinin hastalığa duyarlık açısından önemli etkilerinin olduğu bilinmektedir. Öte yandan, çok sayıdaki çalışmaya karşın prion proteininin patolojik ve fizyolojik koşullardaki rolleri tam olarak belirlenememiştir. Bu derlemede, prion proteinlerinin yapısal özellikleri, hücre içi trafiği, olası fizyolojik rolleri ve apoptozis ile ilişkisi özetlenmiştir. Anahtar Kelimeler-Apoptozis, Prion proteini, Protein yanlış katlanması, Sinyal transdüksiyonu. Biology of PrionProteins AbstractThe common trait of neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's, and prion diseases is accumulation of specific misfolded proteins and forming of large amyloid fibrils or plaques. Recent findings indicate that small soluble oligomers are primary causes of the neuronal dysfunction. Prion protein, a glycosylphosphatidylinositol (GPI)-anchored cellular glycoprotein, have a fundamental role in human and animal prion diseases known as transmissible spongiform encephalopathies (TSEs). In prion diseases, cellular form (PrP C ) of protein may convert into pathogen isoform (PrP Sc ). In the course of this conversion, molecular strategies used by prion proteins remain unclear however, it is known that cellular and pathological isoforms play a key role in etiology and patholology of the neurodegenerative diseases and that mutations and polymorphisms of prion protein coding genes (Prnp) have an important effect on the susceptibility to disease. On the other hand, despite many efforts, the roles of prion protein in pathological and physiological conditions remain be elusive. This review summarizes the structural features, intracellular traffic, and possible physiological roles of PrP C and its relevance with apoptosis.

show abstract

Misfolding of the prion protein: linking biophysical and biological approaches

Cited by 18 publications

References 130 publications

Prion agent diversity and species barrier

Prion agent diversity and species barrier

Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells

Prion Proteinlerinin Biyolojisi / Biology of Prion Proteins

Contact Info

Product

Resources

About