Bettina Drisaldi
Washington University in St. Louis
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Bettina Drisaldi.
Proceedings of the National Academy of Sciences of the United States of America | 2003
Amie L. Phinney; Bettina Drisaldi; Stephen D. Schmidt; Stan Lugowski; Veronica A. Coronado; Yan Liang; Patrick Horne; Jing Yang; Joannis Sekoulidis; Janaky Coomaraswamy; M. Azhar Chishti; Diane W. Cox; Paul M. Mathews; Ralph A. Nixon; George A. Carlson; Peter St George-Hyslop; David Westaway
Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimers disease amyloid-β (Aβ) peptide. To explore this relationship in vivo, toxic-milk (txJ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Aβ deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive txJ mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Aβ levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS Aβ at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS Aβ burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Aβ peptide.
Journal of Virology | 2003
Roberto Chiesa; Pedro Piccardo; Elena Quaglio; Bettina Drisaldi; San Ling Si-Hoe; Masaki Takao; Bernardino Ghetti; David A. Harris
ABSTRACT Tg(PG14) mice express a prion protein (PrP) with a nine-octapeptide insertion associated with a human familial prion disease. These animals spontaneously develop a fatal neurodegenerative disorder characterized by ataxia, neuronal apoptosis, and accumulation in the brain of an aggregated and weakly protease-resistant form of mutant PrP (designated PG14spon). Brain homogenates from Tg(PG14) mice fail to transmit disease after intracerebral inoculation into recipient mice, indicating that PG14spon, although pathogenic, is distinct from PrPSc, the infectious form of PrP. In contrast, inoculation of Tg(PG14) mice with exogenous prions of the RML strain induces accumulation of PG14RML, a PrPSc form of the mutant protein that is infectious and highly protease resistant. Like PrPSc, both PG14spon and PG14RML display conformationally masked epitopes in the central and octapeptide repeat regions. However, these two forms differ profoundly in their oligomeric states, with PG14RML aggregates being much larger and more resistant to dissociation. Our analysis provides new molecular insight into an emerging puzzle in prion biology, the discrepancy between the infectious and neurotoxic properties of PrP.
The EMBO Journal | 2007
Joel C. Watts; Bettina Drisaldi; Vivian Ng; Jing Yang; Bob Strome; Patrick Horne; Man-Sun Sy; Larry Yoong; Rebecca Young; Peter Mastrangelo; Catherine Bergeron; Paul E. Fraser; George A. Carlson; Howard T.J. Mount; Gerold Schmitt-Ulms; David Westaway
The cellular prion protein, PrPC, is neuroprotective in a number of settings and in particular prevents cerebellar degeneration mediated by CNS‐expressed Doppel or internally deleted PrP (‘ΔPrP’). This paradigm has facilitated mapping of activity determinants in PrPC and implicated a cryptic PrPC‐like protein, ‘π’. Shadoo (Sho) is a hypothetical GPI‐anchored protein encoded by the Sprn gene, exhibiting homology and domain organization similar to the N‐terminus of PrP. Here we demonstrate Sprn expression and Sho protein in the adult CNS. Sho expression overlaps PrPC, but is low in cerebellar granular neurons (CGNs) containing PrPC and high in PrPC‐deficient dendritic processes. In Prnp0/0 CGNs, Sho transgenes were PrPC‐like in their ability to counteract neurotoxic effects of either Doppel or ΔPrP. Additionally, prion‐infected mice exhibit a dramatic reduction in endogenous Sho protein. Sho is a candidate for π, and since it engenders a PrPC‐like neuroprotective activity, compromised neuroprotective activity resulting from reduced levels may exacerbate damage in prion infections. Sho may prove useful in deciphering several unresolved facets of prion biology.
Clinics in Laboratory Medicine | 2003
David A. Harris; Roberto Chiesa; Bettina Drisaldi; Elena Quaglio; Antonio Migheli; Pedro Piccardo; Bernardino Ghetti
We have produced a mouse model of a familial prion disorder by introduction of a transgene that encodes the moPrP homolog of a nine-octapeptide insertional mutant associated with an inherited form of CJD in humans. These mice develop progressive neurologic symptoms, display neuropathologic changes, and accumulate a form of mutant PrP in their brains and peripheral tissues that displays some of the biochemical properties of PrPSc. These mice have been extremely valuable for analyzing the cellular and biochemical mechanisms involved in inherited prion disorders and correlating the appearance of the PrPSc-like form with clinical and neuropathologic findings. Because the mutant protein in the mice is highly neurotoxic but appears to lack infectivity, further analysis of its properties promises to shed new light on the molecular distinction between pathogenic and infectious forms of PrP.
Neurobiology of Aging | 2000
David A. Harris; Roberto Chiesa; Bettina Drisaldi; Elena Quaglio; Antonio Migheli; Pedro Piccardo; Bernardino Ghetti
We have generated lines of transgenic mice that express a mutant prion protein containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia. These mice develop an ataxic illness that begins at 65 days of age when the transgene array is homozygous, and results in death by 115-138 days. Starting from birth, mutant PrP is converted into a protease-resistant and detergent-insoluble form that resembles PrP(Sc), and this form accumulates dramatically in many brain regions throughout the lifetime of the mice. As PrP accumulates, there is massive apoptosis of cerebellar granule cells, as well as astrocytosis and deposition of PrP in a punctate pattern. These results establish a new transgenic animal model of an inherited human prion disease, and provide important insights into the molecular pathogenesis of these disorders.
Journal of Biological Chemistry | 2003
Bettina Drisaldi; Richard S. Stewart; Cheryl Adles; Leanne R. Stewart; Elena Quaglio; Emiliano Biasini; Luana Fioriti; Roberto Chiesa; David A. Harris
Proceedings of the National Academy of Sciences of the United States of America | 2000
Roberto Chiesa; Bettina Drisaldi; Elena Quaglio; Antonio Migheli; Pedro Piccardo; Bernardino Ghetti; David A. Harris
Molecular Biology of the Cell | 2001
Richard S. Stewart; Bettina Drisaldi; David A. Harris
Archive | 2007
Joel C. Watts; Bettina Drisaldi; Vivian Ng; Jing Yang; Bob Strome; Patrick Horne; Larry K.K. Yoong; Rebecca Young; Peter Mastrangelo; Catherine Bergeron; Paul E. Fraser; Howard T.J. Mount; Gerold Schmitt-Ulms; David Westaway
Alzheimers & Dementia | 2006
Sun-Kyong Lee; Erwan Paitel; Bettina Drisaldi; Agnès Petit; Stephen D. Schmidt; Paul M. Mathews; Fusheng Chen; Paul E. Fraser; Peter St George-Hyslop; Laurent Meijer; David Westaway