Kevin Tanaka

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It is not clear how Alzheimer amyloid precursor proteins (APP) are metabolized in the brain itself. Secretory forms of APP in a phosphate buffer-soluble fraction were purified from post-mortem human brain by heparin-affinity and ion-exchange chromatography and analyzed by N-terminal amino acid sequencing and SDS polyacrylamide gel(More)
TH17 cells enter tissues to facilitate pathogenic autoimmune responses, including multiple sclerosis (MS). However, the adhesion molecules involved in the unique migratory capacity of TH17 cells, into both inflamed and uninflamed tissues remain unclear. Herein, we characterize MCAM (CD146) as an adhesion molecule that defines human TH17 cells in the(More)
INTRODUCTION Inhibition of gamma-secretase presents a direct target for lowering Aβ production in the brain as a therapy for Alzheimer's disease (AD). However, gamma-secretase is known to process multiple substrates in addition to amyloid precursor protein (APP), most notably Notch, which has limited clinical development of inhibitors targeting this enzyme.(More)
Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with Mr 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized. Cerebral PS-1 were(More)
A panel of antibodies raised against various regions of human presenilin 1(PS1)--the amino-terminal domain, the domain between the transmembrane domains 1 and 2, the cleavage-site, loop domains, or carboxyl-terminal domain--was prepared to analyze PS1 in human tissues. We observed the predominance of two fragments (28-kDa NH2 and 18-kDa COOH fragments) in(More)
Tyrosine hydroxylase (TH) catalyses the rate-limiting step in the biosynthesis of catecholamines. TH expression is regulated in a tissue-specific manner during neuronal development and differentiation. Because of its key regulatory role in central and peripheral catecholamine synthesis, TH is associated with the pathogenesis of several neurological and(More)
Missense mutations in the presenilin-1 (PS-1) gene are known to be responsible for early-onset familial Alzheimer's disease (AD). The normal physiological functions of PS-1 are still incompletely understood, although data on the intracellular localization of PS-1 are accumulating, indicating that it exists mainly in endoplasmic reticulum and Golgi(More)
Production of the soluble amyloid beta-protein (A beta) precedes abnormal accumulation of A beta amyloid in the brains of subjects with Alzheimer's disease. To determine the cellular source and generating mechanisms of soluble A beta in the human brain, we separated an axoplasm fraction from the cerebral white matter and analyzed it. The axoplasm fraction(More)
To elucidate the metabolic process generating amyloid-beta protein (A beta) from beta-amyloid precursor protein (APP) in human brain, we partially purified secretory forms and carboxyl-terminal fragments (CTFs) of APP from the white matter of a Down's syndrome brain. We obtained secretory forms of APP which lack the entire A beta sequence and CTFs which(More)
To elucidate the metabolic process of beta-amyloid precursor proteins (APP) in cerebral gray and white matter of the human brain, we compared the content and characteristics of secretory APP between these two parts. The white matter contained much more secretory APP than the gray matter in both a control and a Down's syndrome brain, but no difference in the(More)
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