Hiroshi Mori on A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo.

COMMENT The critique about Aβ oligomers in our paper is certainly an important issue since Aβ oligomers were clearly declared as the possible cause of Alzheimer disease (Selkoe, 2002). The biochemical nature of Aβ oligomers was not discussed thoroughly in our ...

Hiroshi Mori on Aberrant activation of focal adhesion proteins mediates fibrillar amyloid beta-induced neuronal dystrophy.

COMMENT This clearly demonstrates the involvement of amyloid in potent dystrophic neurite or curly fibre formation as seen in AD. Although it remains to clarify the chemical structure of amyloid b-protein, i.e., fiber, oligomeric or beta-structure, a link between ...

Hiroshi Mori on The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility.

COMMENT This provides a new insight in protein-degradation study as wellas Parkinson's Disease. It is more interesting how the varations of UCH-L1 affect both activities. mori 0 ...

Hiroshi Mori on Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric.

COMMENT More analyses on mutations near alpha-site are welcome because they should contribute to the whole pathological understanding of Abeta metabolism together with beta- and gamma-site cleavages. mori 0 ...

Hiroshi Mori on Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw).

COMMENT In spite of specificity of nicotine in light of AchR, this study may suggest a new clue in etiology as well as treatment. mori 0 ...

Hiroshi Mori on Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia.

COMMENT Tauopathy is an attractive study for the late AD pathogenesis and the effect of apoE e4 allele because the initial report published by Roses, A. and his colleagues described the enhancement of deposition of apoE by the binding of tau. mori 0 ...

Hiroshi Mori on Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia.

COMMENT Tauopathy is an attractive study for the late AD pathogenesis and the effect of apoE e4 allele because the initial report published by Roses, A. and his colleagues described the enhancement of deposition of apoE by the binding of tau. mori 0 ...

Hiroshi Mori on New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage.

COMMENT It is an unexpected finding of the occurrence of an inhibitor to block APP-gamma secretase but not Notch processing. Although we do not know the physiological function of the soluble secreted amyloid protein, it is now potent to exclusively regulate APP ...

Hiroshi Mori on Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1.

COMMENT Further evidence is provided here to prove that PS1 is gamma-secretase. The next proof desired is a direct one. mori 0 ...

Hiroshi Mori on The presence of isoaspartic acid in beta-amyloid plaques indicates plaque age.

COMMENT The presence of racemized amino acid in amyloid may be important for plaque in a stable form but not in an equilibrium form. mori 0 ...

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

COMMENT This nice paper evokes another question and mechanism on Abeta and APP-CT whether toxic Aβ affects APP to enhance the production of APP-C58 as a downstream effector. mori 0 ...

Hiroshi Mori on Notch1 and amyloid precursor protein are competitive substrates for presenilin1-dependent gamma-secretase cleavage.

COMMENT "This may suggests an important clue to understand the physiological interaction, though indirect, between APP and Notch as the common substrate for PS. It must be co crucial if the PS content as an enzyme is constant. However, it still remains if ...

Hiroshi Mori on Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles.

COMMENT "The mechanism for tauopathy must be elucidated and accumulated from multiple attacks. This article must be one of attractive targets though it is not established whether a fly cell is suitable for a model for human neurodegeneration in FTD brains. ...

Hiroshi Mori on The Alzheimer amyloid precursor protein (APP) and FE65, an APP-binding protein, regulate cell movement.

COMMENT "This is an interesting paper to show the physiological function of FE65 in cell movement and signal transduction. More related studies are expected to clarify an unknown activity of APP." mori 0 ...

Hiroshi Mori on The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta -amyloid precursor protein (APP) substrate.

COMMENT "This presents a crucial result on the localization and function for BACE but the question remains open whether all of APP is not digested by BACE in distal Golgi membrane, ER, endosome or plasma membrane." mori 0 ...