Philippe Marambaud on Gain or Loss of Function—Time to Shake up Assumptions on γ-Secretase in Alzheimer Disease?
COMMENT Davies's and Gabrielle Strobel’s comments. The debate is about defining the effect of FAD-linked PS1
11158 RESULTS
COMMENT Davies's and Gabrielle Strobel’s comments. The debate is about defining the effect of FAD-linked PS1
COMMENT These two new studies find that deletions in mitochondrial DNA (mtDNA) accumulate with aging, and are found at very high levels in dopamine-producing neurons within the substantia nigra. These are very important studies since they may account for the age-
COMMENT Two interesting papers recently published in Nature Genetics describe the discovery of somatically occurring deletions in the mitochondrial genome in single cells within the substantia nigra. The manuscript by Bender et al. shows that there is an unexpect
COMMENT Do presenilin enhancer 2 (PEN-2) and presenilin 2 (PS2) cytosolic loops have something in common? In this paper, Cai et al. report the initiation and acceleration of cellular apoptosis by a 22-mer peptide that is usually generated by presenilinase and cas
COMMENT The extreme scarcity of autophagic vacuoles in normal brain and their appearance in states of disease have previously led many to assume that autophagy in neurons is mainly an inducible process. Autophagy is solely responsible for organelle turnover, howe
COMMENT Loss of What? These three papers provide convincing evidence that familial PS mutations can reduce total Aβ production both in vitro and in vivo despite increasing the Aβ42:40 ratio, as a result of decreasing absolute levels of Aβ40. This finding extends
COMMENT I would just like to comment on the questions/remarks that followed our article. First and
COMMENT The publication of this first genome-wide single nucleotide polymorphism (SNP) association study in Parkinson disease (PD) has created considerable debate in the field. The most public parts of this discussion include four follow-up articles (Clarimon et
COMMENT With respect to Dr. Davies's comments, I think first and foremost we have to consider the
COMMENT I think we in this field have to be careful with overinterpreting phenomena in our APP mouse models. Transgenic mouse models expressing AD-associated mutant forms of the amyloid-β precursor protein (APP), or both mutant APP and mutant presenilin-1 (PS1),
COMMENT using brain-specific PS conditional knockout mice (Saura et al., 2004; see Jie Shen´s comment). In that
COMMENT The extremely small size of nerve terminals is one of the major handicaps to studying synaptic function in the brain. That problem gets even more challenging when studying the life cycle of synaptic vesicles, tiny membrane-bound organelles (~40 nm in diam
COMMENT The paper by Darios and Davletov provides significant information on the triggers of cell membrane expansion underlying neurite outgrowth. The importance of omega-3 and omega-6 polyunsaturated fatty acids in enabling syntaxin 3 to complex with SNAP25—even
COMMENT This is a very interesting paper. It indicates that loss of PS1 function may lead to plaque pathology and amyloid depositions. The authors conclude that it is the loss of the γ-secretase function of PS1 and the reduction of Aβ1-40 that lead to increased p
COMMENT We read this interesting paper, which offers a novel mechanism of action for PUFA-mediated neurite outgrowth. The mechanism involves fatty acid modulation of formation of syntaxin 3 complexes with SNARE proteins. The latter are required for regulating fus