Bruno Martoglio on Presenilin—Guilty of Proteolysis by Association?

COMMENT We are pleased that Bart de Strooper and Sangram Sisodia commented on our Science paper in the

Sangram Sisodia on "Cat"egorical Evidence for Presenilin's Proteolytic Role?

COMMENT The manuscript by Zheng et al. reports that the aspartate aa 257 in transmembrane domain six is indispensable for Notch processing and Aβ production. The authors also tested the possibility that expression of a thy1 promoter-driven PS1 transgene encoding

Sangram Sisodia on Presenilin—Guilty of Proteolysis by Association?

COMMENT The Martoglio paper describes the identification human SPP. The experiments are solid. The question at hand is whether the sequence homology within the SPP and PS transmembrane domains that harbor the presumptive catalytic aspartate residues now "pro

John Hardy on tau Exon 10 expression involves a bipartite intron 10 regulatory sequence and weak 5' and 3' splice sites.

COMMENT This is an interesting and thorough paper discussing the details of tau splicing regulation. However, it comes to the suprising, and probably erroneous conclusion that there is not a stem look structure at the exon 10 splice site, but rather, that the lin

Edward Koo on Amyloid-lowering isocoumarins are not direct inhibitors of gamma-secretase.

COMMENT Continuing debate about gamma-secretase cleavage: is APP and notch cleavage by one and the complex or not. This debate will go on for a while. 0 edkoo

Benjamin Wolozin on Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer's disease and Parkinson's disease.

COMMENT This is an interesting article becuase it provides a common mechanism of toxicity for many different aggregated proteins. The link between synuclein and iron is particularly interesting because we have shown that synuclein readily binds iron and forms agg

Benjamin Wolozin on The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells.

COMMENT Investigators such as Luciano D'Adamio and Rachel Neve have both argued for several years that the C-terminus of APP is toxic, and plays an important role the pathophysiology of Alzheimer's disease. The discovery by Sudhoff's group that APP

Benjamin Wolozin on A polymorphic gene nested within an intron of the tau gene: implications for Alzheimer's disease.

COMMENT The discovery of a new gene in the tau gene locus is clearly of interest. Given that the expression patterns of tau and STH are similar to that of tau, it will be of interest to determine whether it is also involved in the regulation of microtubule format

Benjamin Wolozin on Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes.

COMMENT Alpha-synuclein inclusions are associated with a number of different neurodegenerative diseases that are grouped under the term, synucleinopathies. The type of cell that develops inclusions and the type of cell that degenerates differs among each synuclei

Peter Reinhart on Dynamitin in Motor Neurons: Dynamite for ALS Research?

COMMENT On the Davis paper: The combination of technologies used to identify proteins that play a role in synapse retraction is innovative and powerful. This group has taken advantage of the wealth of information provided by yeast genetics about the identity of g

Philip Wong on The Limits of Compensation: Double Loss of Proteases Causes Massive Neuronal Death

COMMENT While there may be some evidence that cathepsins might share some BACE1-like properties, our BACE1 KO neurons/mice clearly demonstrated that it is unlikely there exist other BACE1 homologues as far as processing AbPP is concerned. Moreover, there is no ev

David Holtzman on Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis.

COMMENT In the paper, serum amyloid P is depleted from plasma with a new drug. While SAP has nothing to do with Abeta (it binds to other amyloids in peripheral amyloidosis), it raises the possibility as to whether one can deplete an Aβ binding protein such as apo

NotInMemDB Member on The apolipoprotein E gene, attention, and brain function.

COMMENT Alzheimer disease (AD) is defined by verbal memory loss in its early stages. However, changes in attention also occur. The study of attention in Alzheimer disease may have both theoretical and practical relevance (Della Sala, 2001). Sund et al. extensivel

NotInMemDB Member on Do neuropsychological tests detect preclinical Alzheimer's disease: individual-test versus cognitive-discrepancy score analyses.

COMMENT Charcot noted that pathological aging was associated with cerebral atrophy, and commented that

Edward Koo on Filamentous phage as vector-mediated antibody delivery to the brain.

COMMENT Certainly a different approach to visualize plaques in vivo. Can this ever be used in humans? 0 edkoo