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Prion Transmission (prion + transmission)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Prion domain interaction responsible for species discrimination in yeast [PSI+] transmission

GENES TO CELLS, Issue 12 2003
Hideyuki Hara
Background:, The yeast [PSI+] factor is transmitted by a prion mechanism involving self-propagating Sup35 aggregates. As with mammalian prions, a species barrier prevents prion transmission between yeast species. The N-terminal of Sup35 of Saccharomyces cerevisiae, necessary for [PSI+], contains two species-signature elements,a Gln/Asn-rich region (residues 1,41; designated NQ) that is followed by oligopeptide repeats (designated NR). Results:, In this study, we show that S. cerevisiae[PSI+] is transmissible through plasmid shuffling and cytoplasmic transfer to heterotypic Sup35s whose NQ is replaced with the S. cerevisiae NQ. In addition to homology, the N-terminal location is essential for NQ mediated susceptibility to [PSI+] transmission amongst heterotypic Sup35s. In vitro, a swap of NQ of S. cerevisiae Sup35 led to cross seeding of amyloid formation. Conclusions:, These findings suggest that NQ discriminates self from non-self, and is sufficient to initiate [PSI+] transmission irrespective of whether NR is heterotypic. NR as well as NQ alone coalesces into existing [PSI+] aggregates, showing their independent potentials to interact with the identical sequence in the [PSI+] conformer. The role of NQ and NR in [PSI+] prion formation is discussed. [source]

Genetic and epigenetic control of the efficiency and fidelity of cross-species prion transmission

MOLECULAR MICROBIOLOGY, Issue 6 2010
Buxin Chen
Summary Self-perpetuating amyloid-based protein isoforms (prions) transmit neurodegenerative diseases in mammals and phenotypic traits in yeast. Although mechanisms that control species specificity of prion transmission are poorly understood, studies of closely related orthologues of yeast prion protein Sup35 demonstrate that cross-species prion transmission is modulated by both genetic (specific sequence elements) and epigenetic (prion variants, or ,strains') factors. Depending on the prion variant, the species barrier could be controlled at the level of either heterologous co-aggregation or conversion of the aggregate-associated heterologous protein into a prion polymer. Sequence divergence influences cross-species transmission of different prion variants in opposing ways. The ability of a heterologous prion domain to either faithfully reproduce or irreversibly switch the variant-specific prion patterns depends on both sequence divergence and the prion variant. Sequence variations within different modules of prion domains contribute to transmission barriers in different cross-species combinations. Individual amino acid substitutions within short amyloidogenic stretches drastically alter patterns of cross-species prion conversion, implicating these stretches as major determinants of species specificity. [source]

Reduction of Allodynia by Intrathecal Transplantation of Microencapsulated Porcine Chromaffin Cells

ARTIFICIAL ORGANS, Issue 3 2009
Yu Mi Kim
Abstract Bovine chromaffin cells (BCCs) are well known to have analgesic effect to reduce acute or chronic pain when transplanted in the subarachnoid space and have been considered as an alternative therapy for pain management. However, due to recent concerns over risks associated with prion transmission, porcine tissue is considered to be an alternate xenogeneic source for clinical use. In the present study, we investigated whether microencapsulated porcine adrenal medullary chromaffin cells (PCCs) also have analgesic effect to reduce allodynia caused by neuropathic pain in chronic constriction injury model of rat. PCCs were isolated from a porcine adrenal medulla and then microencapsulated with alginate and poly. In in vitro tests, the microencapsulated PCCs were investigated whether they have an ability to release catecholamines responding to nicotine stimulation. The levels of catecholamines released from the microencapsulated PCCs were significantly higher than from microencapsulated BCCs. In addition, the microencapsulated PCCs released catecholamines and met-enkephalin responding to cerebral spinal fluid (CSF) retrieved from a neuropathic pain model. In in vivo tests, implantation of microencapsulated PCCs reduced both mechanical and cold allodynia in chronic constriction injury model of a rat whereas the microencapsulated BCCs reduced only cold allodynia under the same conditions. The injection of antagonist of opioid peptides reversed the reduction of cold allodynia in microencapsulated PCC-received animal. The levels of catecholamines in the CSF of rats after implantation of microencapsulated PCCs were significantly higher than in the control group. These data suggest that microencapsulated PCCs may be another effective source for the treatment of neuropathic pain. [source]