Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas.

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrPC) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrPC can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness. Nevertheless, the exact molecular mechanisms through which PRNP/PrPC modulates key aspects of GBM biology remain elusive. METHODS: To elucidate the implications of PRNP/PrPC in the biology of this cancer, we analyzed publicly available RNA sequencing (RNA-seq) data of patient-derived GBMs from four independent studies. First, we ranked samples profiled by bulk RNA-seq as PRNPhigh and PRNPlow and compared their transcriptomic landscape. Then, we analyzed PRNP+ and PRNP- GBM cells profiled by single-cell RNA-seq to further understand the molecular context within which PRNP/PrPC might function in this tumor. We explored an additional proteomics dataset, applying similar comparative approaches, to corroborate our findings. RESULTS: Functional profiling revealed that vesicular dynamics signatures are strongly correlated with PRNP/PrPC levels in GBM. We found a panel of 73 genes, enriched in vesicle-related pathways, whose expression levels are increased in PRNPhigh/PRNP+ cells across all RNA-seq datasets. Vesicle-associated genes, ANXA1, RAB31, DSTN and SYPL1, were found to be upregulated in vitro in an in-house collection of patient-derived GBM. Moreover, proteome analysis of patient-derived samples reinforces the findings of enhanced vesicle biogenesis, processing and trafficking in PRNPhigh/PRNP+ GBM cells. CONCLUSIONS: Together, our findings shed light on a novel role for PrPC as a potential modulator of vesicle biology in GBM, which is pivotal for intercellular communication and cancer maintenance. We also introduce GBMdiscovery, a novel user-friendly tool that allows the investigation of specific genes in GBM biology.

Modulation of p53 and prion protein aggregation by RNA.

Several RNA-binding proteins undergo reversible liquid-liquid phase transitions, which, in pathological conditions, might evolve into transitions to solid-state phases, giving rise to amyloid structures. Amyloidogenic and prion-like proteins, such as the tumor suppressor protein p53 and the mammalian prion protein (PrP), bind RNAs specifically or nonspecifically, resulting in changes in their propensity to undergo aggregation. Mutant p53 aggregation seems to play a crucial role in cancer through loss of function, negative dominance and gain of function. PrP conversion modulated by RNA results in highly toxic aggregates. Here, we review data on the modulatory action of RNAs on the aggregation of both proteins.

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease.

Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease / Elevada variabilidade fenotípica na doença de Gerstmann-Sträussler-Scheinker

ABSTRACT Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

RESUMO A doença de Gerstmann-Sträussler-Scheinker é uma doença priônica genética, cuja mutação mais frequente é p.Pro102Leu. Descrevem-se dados clínicos, moleculares e neuropatológicos de sete indivíduos em duas famílias não relacionadas com p.Pro102Leu. Diferenças notáveis entre os pacientes em relação à idade de início, duração da doença e apresentação clínica foram encontradas. Na primeira família, dois pacientes apresentaram demência rapidamente progressiva e três apresentaram fenótipo de ataxia com idade variáveis de início e duração da doença. Nesta família, a idade de início entre mãe e filha diferiu em 39 anos. Na segunda família, fenótipos diferentes foram observados e idades precoces de início dos sintomas foram associadas à heterozigose no códon 129. Não houve diferença em relação ao genótipo do gene da apoE. O genótipo do códon 129 não foi responsável pela variabilidade clínica; heterozigose no códon 129 esteve associada ao início precoce da doença. O exame neuropatológico em dois pacientes confirmou presença de placas típicas e imunohistoquímica para PrPsc.

Genomic analysis and comparison of Pakistani camels (Camelus dromedarius) by prion gene

Background: In many parts of the Old World, domesticated camels (genus - Camelus) are an essential resource, providing food, labor, commodities, and sport to millions of people Of the three extent species, two have been domesticated (singlehumped dromedarius, Camelus dromedarius, and two humped Bactrian camels Camelus bactrianus) and one remains wild (two-humped wild Bactrian camels Camelus ferus). All three species possess a variety adaptations to harsh desert conditions, including mechanisms to tolerate of extreme temperatures, dehydration, and sandy terrain. People residing in harsh climate zones of the world are being benefitted by raising camels in terms of draft, milk, meat, hides and wool from centuries. There are different breeds of dromedary camels distributed in various parts of Pakistan; however there have been scarcity of research work on camels in Pakistan. Identification of novel link between Camel breeders with fatal neurodegenerative disorders is presence or not can be detect by a Prion gene and it was not carried out in Pakistan soil to date. Prion diseases which are a group of fatal neurodegenerative disorders affect both animals and humans. It is believed that the prions are infectious agents responsible for transmissible spongiform encephalopathies. In this study we report the first study on Prion protein gene in dromedary camels of Pakistan. Material, Methods & Results: Genes are the blueprint of life and determine the functional aspects of cellular mechanisms. Genomic DNA of the enrolled blood samples was extracted using the Nucleospin® DNA extraction kit. Genomic DNA was run on Agarose gel electrophoresis, checked the Genomic DNA quality and amplified using prion region specific primer pair. Prion protein gene was amplified (770 bp) in 35 individuals of seven dromedary camel breeds from the province...[...](AU)

Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature.

Although prion diseases are generally thought to present as rapidly progressive dementias with survival of only a few months, the phenotypic spectrum for genetic prion diseases (gPrDs) is much broader. The majority have a rapid decline with short survival, but many patients with gPrDs present as slowly progressive ataxic or parkinsonian disorders with progression over a few to several years. A few very rare mutations even present as neuropsychiatric disorders, sometimes with systemic symptoms such as gastrointestinal disorders and neuropathy, progressing over years to decades. gPrDs are caused by mutations in the prion protein gene (PRNP), and have been historically classified based on their clinicopathological features as genetic Jakob-Creutzfeldt disease (gJCD), Gerstmann-Sträussler-Scheinker (GSS), or Fatal Familial Insomnia (FFI). Mutations in PRNP can be missense, nonsense, and octapeptide repeat insertions or a deletion, and present with diverse clinical features, sensitivities of ancillary testing, and neuropathological findings. We present the UCSF gPrD cohort, including 129 symptomatic patients referred to and/or seen at UCSF between 2001 and 2016, and compare the clinical features of the gPrDs from 22 mutations identified in our cohort with data from the literature, as well as perform a literature review on most other mutations not represented in our cohort. E200K is the most common mutation worldwide, is associated with gJCD, and was the most common in the UCSF cohort. Among the GSS-associated mutations, P102L is the most commonly reported and was also the most common at UCSF. We also had several octapeptide repeat insertions (OPRI), a rare nonsense mutation (Q160X), and three novel mutations (K194E, E200G, and A224V) in our UCSF cohort. © 2016 Wiley Periodicals, Inc.

Genomic analysis and comparison of Pakistani camels (Camelus dromedarius) by prion gene

Background: In many parts of the Old World, domesticated camels (genus - Camelus) are an essential resource, providing food, labor, commodities, and sport to millions of people Of the three extent species, two have been domesticated (singlehumped dromedarius, Camelus dromedarius, and two humped Bactrian camels Camelus bactrianus) and one remains wild (two-humped wild Bactrian camels Camelus ferus). All three species possess a variety adaptations to harsh desert conditions, including mechanisms to tolerate of extreme temperatures, dehydration, and sandy terrain. People residing in harsh climate zones of the world are being benefitted by raising camels in terms of draft, milk, meat, hides and wool from centuries. There are different breeds of dromedary camels distributed in various parts of Pakistan; however there have been scarcity of research work on camels in Pakistan. Identification of novel link between Camel breeders with fatal neurodegenerative disorders is presence or not can be detect by a Prion gene and it was not carried out in Pakistan soil to date. Prion diseases which are a group of fatal neurodegenerative disorders affect both animals and humans. It is believed that the prions are infectious agents responsible for transmissible spongiform encephalopathies. In this study we report the first study on Prion protein gene in dromedary camels of Pakistan. Material, Methods & Results: Genes are the blueprint of life and determine the functional aspects of cellular mechanisms. Genomic DNA of the enrolled blood samples was extracted using the Nucleospin® DNA extraction kit. Genomic DNA was run on Agarose gel electrophoresis, checked the Genomic DNA quality and amplified using prion region specific primer pair. Prion protein gene was amplified (770 bp) in 35 individuals of seven dromedary camel breeds from the province...[...]

Polymorphisms in the Prion Protein Gene of cattle breeds from Brazil / Polimorfismos no gene da proteína priônica em bovinos no Brasil

One of the alterations that occur in the PRNP gene in bovines is the insertion/deletion (indel) of base sequences in specific regions, such as indels of 12-base pairs (bp) in intron 1 and of 23- bp in the promoter region. The deletion allele of 23 bp is associated with susceptibility to bovine spongiform encephalopathy (BSE) as well as the presence of the deletion allele of 12 bp. In the present study, the variability of nucleotides in the promoter region and intron 1 of the PRNP gene was genotyped for the Angus, Canchim, Nellore and Simmental bovine breeds to identify the genotype profiles of resistance and/or susceptibility to BSE in each animal. Genomic DNA was extracted for amplification of the target regions of the PRNP gene using polymerase chain reaction (PCR) and specific primers. The PCR products were submitted to electrophoresis in agarose gel 3% and sequencing for genotyping. With the exception of the Angus breed, most breeds exhibited a higher frequency of deletion alleles for 12 bp and 23 bp in comparison to their respective insertion alleles for both regions. These results represent an important contribution to understanding the formation process of the Brazilian herd in relation to bovine PRNP gene polymorphisms.(AU)

Uma das mudanças que ocorrem no gene PRNP em bovinos é a inserção e/ou deleção (indels) de sequências de bases, em determinadas regiões como, por exemplo, as indels de 12 pares de bases (pb) no íntron 1 e 23pb na região promotora. O alelo de deleção de 23pb está relacionado com a suscetibilidade à Encefalopatia Espongiforme Bovina (EEB), assim como a presença do alelo de deleção de 12pb. Neste estudo foi genotipada a variabilidade de nucleotídeos da região promotora e íntron 1 do gene PRNP em bovinos das raças Angus, Canchim, Nelore e Simental, para identificar os perfis genotípicos de resistência e/ou suscetibilidade à EEB de cada animal. Foi realizada a extração de DNA genômico para amplificação das regiões alvo do gene PRNP, por meio da reação em cadeia de polimerase (PCR) utilizando-se primers específicos. Os produtos da PCR foram submetidos à eletroforese em gel de agarose a 3%, e sequenciamento para a realização da genotipagem. Com exceção da raça Angus, a maioria das raças apresentaram maiores frequências do alelo de deleção tanto para 12pb como 23pb, em comparação com seus respectivos alelos de inserção, para as duas regiões. Esses resultados abrem caminhos para o conhecimento de como o rebanho brasileiro está sendo formado com relação aos polimorfismos do gene PRNP bovino.(AU)

Polymorphisms in the Prion Protein Gene of cattle breeds from Brazil / Polimorfismos no gene da proteína priônica em bovinos no Brasil

One of the alterations that occur in the PRNP gene in bovines is the insertion/deletion (indel) of base sequences in specific regions, such as indels of 12-base pairs (bp) in intron 1 and of 23- bp in the promoter region. The deletion allele of 23 bp is associated with susceptibility to bovine spongiform encephalopathy (BSE) as well as the presence of the deletion allele of 12 bp. In the present study, the variability of nucleotides in the promoter region and intron 1 of the PRNP gene was genotyped for the Angus, Canchim, Nellore and Simmental bovine breeds to identify the genotype profiles of resistance and/or susceptibility to BSE in each animal. Genomic DNA was extracted for amplification of the target regions of the PRNP gene using polymerase chain reaction (PCR) and specific primers. The PCR products were submitted to electrophoresis in agarose gel 3% and sequencing for genotyping. With the exception of the Angus breed, most breeds exhibited a higher frequency of deletion alleles for 12 bp and 23 bp in comparison to their respective insertion alleles for both regions. These results represent an important contribution to understanding the formation process of the Brazilian herd in relation to bovine PRNP gene polymorphisms.(AU)

Uma das mudanças que ocorrem no gene PRNP em bovinos é a inserção e/ou deleção (indels) de sequências de bases, em determinadas regiões como, por exemplo, as indels de 12 pares de bases (pb) no íntron 1 e 23pb na região promotora. O alelo de deleção de 23pb está relacionado com a suscetibilidade à Encefalopatia Espongiforme Bovina (EEB), assim como a presença do alelo de deleção de 12pb. Neste estudo foi genotipada a variabilidade de nucleotídeos da região promotora e íntron 1 do gene PRNP em bovinos das raças Angus, Canchim, Nelore e Simental, para identificar os perfis genotípicos de resistência e/ou suscetibilidade à EEB de cada animal. Foi realizada a extração de DNA genômico para amplificação das regiões alvo do gene PRNP, por meio da reação em cadeia de polimerase (PCR) utilizando-se primers específicos. Os produtos da PCR foram submetidos à eletroforese em gel de agarose a 3%, e sequenciamento para a realização da genotipagem. Com exceção da raça Angus, a maioria das raças apresentaram maiores frequências do alelo de deleção tanto para 12pb como 23pb, em comparação com seus respectivos alelos de inserção, para as duas regiões. Esses resultados abrem caminhos para o conhecimento de como o rebanho brasileiro está sendo formado com relação aos polimorfismos do gene PRNP bovino.(AU)

Mammalian prion protein (PrP) forms conformationally different amyloid intracellular aggregates in bacteria.

BACKGROUND: An increasing number of proteins are being shown to assemble into amyloid structures that lead to pathological states. Among them, mammalian prions outstand due to their ability to transmit the pathogenic conformation, becoming thus infectious. The structural conversion of the cellular prion protein (PrP(C)), into its misfolded pathogenic form (PrP(Sc)) is the central event of prion-driven pathologies. The study of the structural properties of intracellular amyloid aggregates in general and of prion-like ones in particular is a challenging task. In this context, the evidence that the inclusion bodies formed by amyloid proteins in bacteria display amyloid-like structural and functional properties make them a privileged system to model intracellular amyloid aggregation. RESULTS: Here we provide the first demonstration that recombinant murine PrP and its C-terminal domain (90-231) attain amyloid conformations inside bacteria. Moreover, the inclusions formed by these two PrP proteins display conformational diversity, since they differ in fibril morphology, binding affinity to amyloid dyes, stability, resistance to proteinase K digestion and neurotoxicity. CONCLUSIONS: Overall, our results suggest that modelling PrP amyloid formation in microbial cell factories might open an avenue for a better understanding of the structural features modulating the pathogenic impact of this intriguing protein.

Expression patterns of Doppel in differential ovine PRNP genotypes: quantification using real-time RT-PCR.

Doppel is a homologue of cellular prion protein (PrP)-like protein (PrPC). Different tissue samples were collected from the central nervous system plus four regions of lymphoid system, eleven regions of digestive tract and two reproductive organs from four ARR/ARQ and four ARH/ARQ sheep, genotypes of the PrP gene. Total RNA was isolated from these samples, and Doppel mRNA was quantified by real-time RT-PCR using SYBR Green. Doppel mRNA expression was higher in the ovary, hypothalamus and brain than in other tissues, and it significantly differed between the two genotypes in brain, ileum, cecum, rectum, colon, and uterus. This study demonstrated that Doppel mRNA expression in sheep with ARR/ARQ or ARH/ARQ genotypes was very different. These findings could be helpful in future studies of the relationship between PrP and Doppel.

Disaggregases, molecular chaperones that resolubilize protein aggregates.

The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.

Activation and function of murine primary microglia in the absence of the prion protein.

The prion protein (PrP(C)) is predominantly expressed in the nervous and immune systems and is involved in relevant cell signaling. Microglia participate in neuroimmune interactions, and their regulatory mechanisms are critical for both health and disease. Despite recent reports with a microglial cell line, little is known about the relevance of PrP(C) in brain microglia. We investigated the role of PrP(C) in mouse primary microglia, and found no differences between wild type and Prnp-null cells in cell morphology or the expression of a microglial marker. Translocation of NF-κB to the nucleus also did not differ, nor did cytokine production. The levels of iNOS were also similar and, finally, microglia of either genotype showed no differences in either rates of phagocytosis or migration, even following activation. Thus, functional roles of PrP(C) in primary microglial cells are - if present - much more subtle than in transformed microglial cell lines.

Report of outbreaks of classical scrapie in Dorper sheep and associated prion protein gene polymorphisms in affected flocks.

Scrapie is an infectious neurodegenerative disease affecting sheep and goats, related with conformational alteration of an isoform of the prion protein that leads to deposition and aggregation in the host's central nervous system. Occurrence of the natural disease can be influenced by host genetic factors, such as a single nucleotide polymorphism of the prion protein gene. This study reports three scrapie-affected Dorper flocks located on three different farms in Brazil. The objective of this study was to analyze these three flocks using scrapie diagnostics, combining histology, immunohistochemistry, genotyping, and western blot assays. For immunohistochemistry, 192 sheep were selected and 308 sheep blood samples were taken for genotyping. A total of 22 sheep were scrapie positive by immunohistochemistry. Of these, four presented clinical signs and had scrapie immunoreactivity at the obex in western blot assays. The sheep without clinical signs were positive in lymphoid organs, such as the third eyelid and rectal mucosa. The major genotypes found on the flocks were ARQ/ARQ, ARQ/ARR, and ARQ/VRQ for codons 136, 154, and 171. Most of the sheep were considered to be at moderate to high risk, based on risk groups for developing scrapie. Some blood samples were sequenced, and polymorphisms were identified in other codons, such as 127, 142, and 143. Our data demonstrate the importance of preclinical scrapie diagnosis in Brazilian sheep, as most of the affected sheep showed no clinical signs, and emphasize the relevance of genotyping other Dorper sheep to determine the genotypic profile of the breed.

Sporadic Creutzfeldt-Jakob disease in a native Puerto Rican patient.

The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most physicians given its extremely low incidence and different clinico-pathological presentations. We report the case of a 56-year old patient native to Puerto Rico suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were notorious for bilateral cortical blindness followed by rapidly progressive cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along with positive brain MRI and EEG, are highly indicative of CJD. The definite diagnosis was confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion protein (PrP) gene, widespread histopathological changes and the accumulation of scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient, admitted to our institution in 2011, represents the first detailed report of sCJD in a native Puerto Rican patient living in Puerto Rico.

Conhecimento e prática dos enfermeiros sobre hanseníase: ações de controle e eliminação / Conocimiento y práctica de enfermeros acerca de hanseniasis: acciones de control y eliminación / Knowledge and practice of the nurse about leprosy: actions of control and elimination

RESUMO Objetivo: avaliar o conhecimento e a prática de enfermeiros da atenção primária de saúde quanto às ações de controle e eliminação da hanseníase. Método: estudo avaliativo, com abordagem qualitativa, utilizando o Discurso do Sujeito Coletivo, cujos dados foram obtidos por meio de entrevista semiestruturada, realizada com 16 enfermeiros. Resultados: os dados coletados revelaram que os profissionais de saúde possuem conhecimento suficiente sobre a Política Nacional de Controle e Eliminação da Hanseníase (PNCEH) e que as principais ações preconizadas foram executadas, porém, a notificação de casos suspeitos ou confirmados e a reinserção social do doente não foram citadas. Conclusão: manter os doentes em tratamento, sobrecarga de trabalho, falta de interdisciplinaridade e tratamento realizado em outros locais fora da comunidade foram dificuldades relatadas pelos profissionais. Os enfermeiros conhecem as ações direcionadas à assistência ao hanseniano, entretanto, o estudo aponta para a necessidade de uma prática mais alinhada ao que preconiza a PNECH. .

RESUMEN Objetivo: evaluar el conocimiento y la práctica de los enfermeros que trabajan en la atención primaria de salud como las acciones de control y eliminación de la hanseniasis. Método: es un estudio evaluativo con enfoque cualitativo, utilizando el Discurso del Sujeto Colectivo, cuyos datos fueron recolectados a través de entrevistas semi-estructuradas con 16 enfermeros. Resultados: los datos obtenidos revelaron que los profesionales de la salud tienen el conocimiento suficiente sobre la Política Nacional de Control y Erradicación de la Hanseniasis (PNCEH) y que las principales acciones recomendadas se han implementado, pero la notificación de los casos sospechosos o confirmados y reinserción social del paciente no fue mencionado. Conclusión: mantener a los pacientes en tratamiento, exceso de trabajo, falta de interdisciplinariedad y tratamiento realizado en otros lugares fuera de la comunidad fueron problemas reportados por el personal de salud. Los enfermeros conocen las acciones destinadas a ayudar a los pacientes con hanseniasis, sin embargo, el estudio apunta la necesidad de una practica más direccionado a lo que defiende la PNECH. .

ABSTRACT Objective: to assess the knowledge and practice of primary health care nurses about control and elimination actions of leprosy. Method: evaluation study with qualitative approach, using the Discourse of the Collective Subject, data were collected through semi-structured interviews conducted with 16 nurses. Results: the data collected revealed that health professionals have suffi cient knowledge about the National Policy on Control and Elimination of Leprosy (NPCEL) and that the main actions preconized were applied, however, notifi cation of suspected or confi rmed cases and social reintegration of the patient were not mentioned. Conclusion: keeping patients in treatment, overload of work, lack of interdisciplinarity and treatment performed at other locations outside of the community were diffi culties reported by professionals. Nurses know the actions addressed at assistance of leprosy patients, however, the study points to the need for a practice which is more aligned to what advocates NPCEL. .

Epidemiological genetics and meta-analysis of a polymorphism at codon 129 of the PRNP gene in Alzheimer's disease in Brazil.

The polymorphism at codon 129 of the prion protein gene (PRNP) is a major risk factor for Creutzfeldt-Jakob disease (CJD). Several authors reported neuropathological and clinical overlapping between CJD and Alzheimer's disease (AD), with a few association studies generating conflicting results. To investigate the distribution of this polymorphism in AD, we selected 58 patients with probable AD and 73 controls from a Brazilian population. There was no association between the PRNP polymorphism at codon 129 and AD. Our meta-analysis (performed using Alzgene; http://www.alzgene.org) along with previous studies conducted in Brazil demonstrated a negative association.

Gerstmann-Sträussler-Scheinker syndrome with variable phenotype in a new kindred with PRNP-P102L mutation.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a dominantly inherited disorder belonging to the group of transmissible human spongiform encephalopathies or prion diseases. Several families affected by GSS with patients carrying mutations in the prion protein gene have been described worldwide. We report clinical, genealogical, neuropathology and molecular study results from two members of the first Argentine kindred affected by GSS. Both family members presented a frontotemporal-like syndrome, one with and the other without ataxia, with different lesions on neuropathology. A Pro to Leu point mutation at codon 102 (P102L) of the prion protein gene was detected in one of the subjects studied. The pathogenic basis of phenotypic variability observed in this family remains unclear, but resembles that observed in other P102L GSS patients from the same family.

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy.

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.

Codon 129 polymorphism of prion protein gene in is not a risk factor for Alzheimer's disease.

UNLABELLED: Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP) codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD). OBJECTIVE: To describe the association between codon 129 polymorphisms and AD. METHODS: We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE) were evaluated. RESULTS: Codon 129 genotype distribution in AD 45.5% methionine (MM), 42.2% methionine valine (MV), 12.1% valine (VV); and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05). There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. CONCLUSION: Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.