43 RESULTS
COMMENT Cryo-electron microscopy (cryo-EM, aka electron cryomicroscopy) has become the go-to tool for determining the molecular architecture of alternatively folded proteins in various disease states. A particular advantage of cryo-EM is that it can be applied to ...
COMMENT I met Dale around 25 years ago, when the Alzheimer’s field was in an uncertain state. Researchers were seeking a clear path to disease modification, but many of the tools that would make this possible were still lacking. Dale and I began a brief and ...
COMMENT Beginning in the 1980s, experiments have shown that prions injected into the eye translocate with high spatial and temporal specificity to downstream components of the visual system (Buyukmihci et al., 1983; Fraser, 1982; Kimberlin et al., 1986; Liberski ...
COMMENT This certainly is an important and thoughtful commentary that keeps us focused on unanswered questions. However, I would take issue with the statement that “the molecular mechanisms of PrP proliferation and neurotoxicity in ‘classical’ prion diseases are ...
COMMENT I think this strategy has considerable value for clarifying how pathogenic protein molecules interact to cause disease. A key question, though, is where the proteins interact in the cell, since this could strongly influence the outcome. For instance, the ...
COMMENT The study by Yetman and colleagues is nicely done, and the resolution of the images is superb. The authors convincingly show that the “leakage” of transgene expression in the Nop-tTA driver line is much more extensive than was previously thought. The ...
COMMENT This is an elegant series of experiments using interesting and informative models. The findings complement a growing literature demonstrating the cell-to-cell spread of pathogenic protein seeds formed by Aβ, PrP, tau, alpha-synuclein, SOD1 and others. ...
COMMENT The prion paradigm has considerable explanatory power for the ontogeny of human neurodegenerative diseases, which mostly appear to emerge from the endogenous misfolding and seeded aggregation of disease-specific proteins. These two papers add to ...
COMMENT These thorough and elegant studies are the strongest evidence yet that seeds of tau protein behave like prions. They compellingly reinforce the prion concept as one of the most important pathogenic principles of our time. But since a prion is defined as ...
COMMENT The data in this study look convincing, and send the encouraging message that tauopathy, an intracellular proteopathy, can indeed be mitigated by an agent that appears to intercept seeds extracellularly. Hence, it may not be necessary for therapeutic ...
COMMENT This paper by Wang et al. is well written and makes a strong case for potentially reversible declines in neuronal function with age. As the authors note, despite their relatively close biological proximity to humans, rhesus monkeys do not develop ...
COMMENT A nice demonstration that the inability of regulatory proteins to enter the nucleus in a functional form causes translational dysregulation and neuronal degeneration (see also the recent ARF story on TDP-43). lwalker 0 ...
COMMENT Two prominent messages emerge from the Sephton paper and the burgeoning literature on TDP-43: 1) TDP-43 is important for the normal functioning of cells; and 2) its actions are many and complex. This being so, is it realistic to assume that targeting one ...
COMMENT The ability of many cell types, both prokaryotic and eukaryotic, to disseminate and retrieve biological material is increasingly apparent. The purpose of such exchange in many instances remains unclear, and in the case of shared pathogenic protein ...
COMMENT A number of proteopathies coexist in the aging human brain, but whether these diseases arise independently or in pathogenic concert remains unclear. In this paper, Morales and colleagues present a reasonably compelling argument that aggregated Aβ and ...
