10 RESULTS
COMMENT This is a provocative and exciting study that addresses the sex-specific effects in Alzheimer’s disease, an understudied topic with important impact on both basic mechanistic and translational efforts. Here, the dissociation of the sex chromosomes and sex ...
COMMENT The proposed signaling cascade—Aβ1-42 induces nitrosylation of GAPDH, which activates p300-mediated tau acetylation on one hand, and inhibits SIRT1-mediated tau deacetylation on the other—provides an interesting mechanism on how Aβ might induce pathogenic ...
COMMENT There are two exciting aspects of this paper. One is the finding that progranulin deficiency (full-length and granulins) leads to gene-dose alterations in lipid metabolism. The effects on lysosomal lipid processing are very compelling, and offer a brand ...
COMMENT This is a very important study and useful resource for the field. This is the first comprehensive, unbiased, quantitative mass-spectrometry analysis of tau modification under normal conditions. The study and analyses are rigorously performed, and the data ...
COMMENT This paper by Mildner et al. showed that CCR2 localized at subsets of myeloid cells exert differential roles in plaque pathology. CCR2 localized on peripheral macrophages is required for their infiltration into AD mouse brain parenchyma after total-body ...
COMMENT Aβ-lowering effects of E64d are very intriguing. However, since E64d inhibits numerous cathepsins, the mechanism by which E64d lowers Aβ remains unclear. Moreover, given the recent finding from Randy Nixon's group that inhibitors of cathepsins, ...
COMMENT I agree that the roles of cysteine proteases in Aβ metabolism deserve in-depth investigation, and findings obtained with both genetic and pharmacological approaches should be evaluated in greater detail. In agreement with Dr. Vassar’s comments, the two ...
COMMENT Bogyo and colleagues developed a new generation of fluorescent quenched activity-based probes that can be used to visualize the dynamics of active proteases in whole animals. These elegant probes combine the “quenching” feature, which offers the advantage ...
COMMENT Dr. Greg Hook commented that the Swedish mutation at the β-secretase site in hAPP may have prevented β-secretase activity of cathepsin B (CatB). We addressed this possibility in our original article (1). Primary cortical neurons from CatB–/– mice and CatB ...
COMMENT Designer Drugs to Target Inflammation in AD With this comment I'll add a component focused on microglia to this discussion. Accumulating evidence supports the role of microglia in neurodegenerative diseases. In AD, microglia activation has been ...
