The prion protein M129V polymorphism

Golanska, Ewa; Sieruta, Monika; Corder, Elizabeth H.; Gresner, Sylwia M.; Pfeffer, Anna; Chodakowska-Żebrowska, Małgorzata; Sobów, Tomasz; Klich, Izabela; Mossakowska, Małgorzata; Szybińska, Aleksandra; Barcikowska, Maria; Liberski, Paweł P.

doi:10.4161/pri.23903

Cited by 6 publications

(4 citation statements)

References 32 publications

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“… 23 The disease also requires methionine (M) at position 129 and is not observed with a valine (V) at position 129, another often found variant of the wild type. 24 In our previous investigation, 18 we considered only the predominant 129M variant of the wild type. Here, we extend these investigations and research on how the residue replacements D178N and M129V alter the interactions between poly-A-RNA and prions and the mechanism that leads to unfolding of helix A.…”

Section: Introductionmentioning

confidence: 99%

“…The disease is associated with a heritable mutation D178N, replacing an acidic aspartic acid (D) by a neutral asparagine (N), which is known to increase the polymorphism of the scrapie form . The disease also requires methionine (M) at position 129 and is not observed with a valine (V) at position 129, another often found variant of the wild type . In our previous investigation, we considered only the predominant 129M variant of the wild type.…”

Section: Introductionmentioning

confidence: 99%

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Mutations Alter RNA-Mediated Conversion of Human Prions

et al. 2018

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Prion diseases are connected with self-replication and self-propagation of misfolded proteins. The rate-limiting factor is the formation of the initial seed. We have recently studied the early stages in the conversion between functional PrPC and the infectious scrapie PrPSC form, triggered by the binding of RNA. Here, we study how this process is modulated by the prion sequence. We focus on residues 129 and 178, which are connected to the hereditary neurodegenerative disease fatal familial insomnia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mutations Alter RNA-Mediated Conversion of Human Prions

et al. 2018

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“…This mutation is implied in fatal familial insomnia where a loss of neurons in the thalamus progressively worsens insomnia and eventually leads to dementia . Note that symptoms of fatal familial insomnia appear only if the prion has methionine (M) at position 129 and is not observed with a valine (V) at position 129, another variant often found in the wild type . Nucleation of the initial seed may also be enhanced by environmental conditions or interaction with other molecules.…”

Section: Introductionmentioning

confidence: 99%

Early Stages of RNA-Mediated Conversion of Human Prions

Lubecka

Hansmann

2022

J. Phys. Chem. B

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Prion diseases are characterized by the conversion of prion proteins from a PrP C fold into a disease-causing PrP SC form that is self-replicating. A possible agent to trigger this conversion is polyadenosine RNA, but both mechanism and pathways of the conversion are poorly understood. Using coarse-grained molecular dynamic simulations we study the time evolution of PrP C over 600 μs. We find that both the D178N mutation and interacting with polyadenosine RNA reduce the helicity of the protein and encourage formation of segments with strand-like motifs. We conjecture that these transient β-strands nucleate the conversion of the protein to the scrapie conformation PrP SC .

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“…While the dementia seen in Creutzfeldt–Jakob disease patients is likely a result of prion protein aggregation, various studies suggest that the PRNP gene is also involved in other forms of dementia, but results are inconsistent ( Rujescu et al , 2003 ; Del Bo et al , 2006 ; Jeong et al , 2007 ; Poleggi et al , 2008 ; Choi et al , 2010 ; Golanska et al , 2013 ; He et al., 2013 ; Zhang et al , 2016 ). Furthermore, studies performed on early cognitive decline and early-ons et Al zheimer’s disease also show inconsistency regarding which of the homozygous carriers have a higher risk ( Croes et al , 2003 ; Dermaut et al , 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Prion protein codon 129 polymorphism in mild cognitive impairment and dementia: the Rotterdam Study

Karamujić‐Čomić

Ahmad

Lysen

et al. 2020

Brain Communications

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Creutzfeldt–Jakob disease is a rare, fatal, neurodegenerative disease caused by the accumulation of abnormally folded prion proteins. The common polymorphism at codon 129 (methionine/valine) in the prion protein (PRNP) gene is the most important determinant of genetic susceptibility. Homozygotes of either allele have a higher risk of sporadic Creutzfeldt–Jakob disease. Various studies suggest that this polymorphism is also involved in other forms of dementia. We studied the association between the codon 129 polymorphism of the PRNP gene and mild cognitive impairment in 3605 participants from the Rotterdam Study using logistic regression analyses. Subsequently, we studied the association between this polymorphism and incident dementia, including Alzheimer’s disease, in 11 070 participants using Cox proportional hazard models. Analyses were adjusted for age and sex. We found the prevalence of mild cognitive impairment to be higher for carriers of the methionine/methionine genotype (odds ratio, 1.40; 95% confidence interval, 1.11–1.78; P = 0.005) as well as for carriers of the valine/valine genotype (odds ratio, 1.37; 95% confidence interval, 0.96–1.97; P = 0.08). The codon 129 polymorphism was not associated with the risk of incident dementia or Alzheimer’s disease. In conclusion, we found a statistically significant higher prevalence of mild cognitive impairment in carriers of the methionine/methionine genotype in the codon 129 polymorphism of the PRNP gene within this population-based study. No associations were found between the codon 129 polymorphism and dementia or Alzheimer’s disease in the general population.

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The prion protein M129V polymorphism

Cited by 6 publications

References 32 publications

Mutations Alter RNA-Mediated Conversion of Human Prions

Mutations Alter RNA-Mediated Conversion of Human Prions

Early Stages of RNA-Mediated Conversion of Human Prions

Prion protein codon 129 polymorphism in mild cognitive impairment and dementia: the Rotterdam Study

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