Edward Koo on Caspase inhibition protects nerve terminals from in vitro degradation.

COMMENT A nice and different way to look at the phenomenon of "synaptosis" first reported by the Cole lab. 0 edkoo

Edward Koo on PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin.

COMMENT The γ-secretase complex gains more integral members necessary for function. Similar results reported at Int'l AD meeting in Sweden this summer but Haass lab wins this sprint! 0 edkoo

Edward Koo on Abnormal cerebellar signaling induces dystonia in mice.

COMMENT While not AD or neurodegeneration, this is a very interesting finding as there are no good models of dystonia. This may be one such model. 0 edkoo

Benjamin Wolozin on Regulation of APP-dependent transcription complexes by Mint/X11s: differential functions of Mint isoforms.

COMMENT Transcriptional activation by APP has become an increasingly current subject and provides important insights into the function of APP. This paper provides a novel set of proteins interacting with APP, and validates the increasing number of papers document

Terrence Town on Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression in macrophages.

COMMENT In continuing their search for novel inhibitors of CD40 expression on macrophages/microglia, Wesemann and colleagues present data showing that SOCS-1 overexpression is able to mitigate IFN-gamma-induced CD40 expression in a macrophage cell line. It seems

Omar El-Agnaf on An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage.

COMMENT Very interesting study to link environmental toxins like rotenone with the development of PD. The development of cellular model of alpha-synuclein aggregation is important to understand the molecular mechanism of alpha-synuclein toxicity and screening for

Chris Exley on β Amyloid Degradation: The Forgotten Half of Alzheimer's Disease

COMMENT The authors might like to note our recent research on Aβ degradation by plasmin, (Exley and Korchazhkina, 2001). I can also add that in research in press in JAD, we have identified a cleavage site for plasmin in Aβ25-35, and we have shown that the activit

Edward Koo on Antibodies to beta-amyloid decrease the blood-to-brain transfer of beta-amyloid peptide.

COMMENT Apparent confirmation of the peripheral sink idea from David Holtzman and Steve Paul? 0 edkoo

Edward Koo on The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration.

COMMENT Interesting localization of abeta at sites of macular degeneration. The Aβ lies outside the retinal pigment epithelium, so I guess this is technically outside the nervous system (?) The authors argue that the abeta may activate local inflammatory response

Ruth Perez on Novel Cell-Based Parkinson's Model Shows Promise

COMMENT The work by Tim Greenamyre, Todd Sherer, and colleagues provides a novel cellular model of chronic environmental toxin exposure that may well be relevant to Parkinson’s disease (PD). Although the authors did not use dopaminergic neurons (which they discus

David Holtzman on Antibodies to beta-amyloid decrease the blood-to-brain transfer of beta-amyloid peptide.

COMMENT This paper is interesting in that it presents direct evidence that an antibody to Abeta in the circulation decreases Aβ transport into the brain. 0 holtzman

David Holtzman on The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration.

COMMENT This is an interesting paper suggesting that components of Drusen may contain Abeta deposits. If true, this may implicate Abeta deposition in macular degeneration. The confocal immunostaining in Fig. 2 of this paper is impressive. My concern is whether th

Benjamin Wolozin on An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage.

COMMENT Developing adequate cell culture models of synuclein aggregation has proved challenging, and this paper makes a significant step forward. It is curious that the process is so slow, given that the cells divide and likely don't exist in the same state

Bruce Yankner on Dopamine Renders α-Synuclein Toxic to Neurons

COMMENT Reply by Bruce Yankner The paper by Perez et al. is quite interesting because it suggests that α-synuclein can downregulate tyrosine hydroxylase activity in a stably transfected dopaminergic cell line. However, this is a cell line that has been selected f

David Holtzman on Mutant Proteins—Is it Quality or Quantity that Counts?

COMMENT It is interesting [that] the authors show that some fraction of genes with allelic variation have differential expression of the alleles present. This theoretically could affect certain disease pathways depending on the genes involved. To my knowledge, th