Toshihide Takeuchi

Intracellular delivery of bioactive molecules using arginine-rich peptides, including oligoarginine and HIV-1 Tat peptides, is a recently developed technology. Here, we report a dramatic change in the methods of internalization for these peptides brought about by the presence of pyrenebutyrate, a counteranion bearing an aromatic hydrophobic moiety. In the absence of pyrenebutyrate, endocytosis plays a major role in cellular uptake. However, the addition of pyrenebutyrate results in direct membra

The heat shock response (HSR), a transcriptional response that up-regulates molecular chaperones upon heat shock, is necessary for cell survival in a stressful environment to maintain protein homeostasis (proteostasis). However, there is accumulating evidence that the HSR does not ubiquitously occur under stress conditions, but largely depends on the cell types. Despite such imbalanced HSR among different cells and tissues, molecular mechanisms by which multicellular organisms maintain their glo

Arginine-rich cell-penetrating peptides (CPPs) including Tat, Penetratin and oligoarginine peptides are a series of short peptides that can be efficiently internalized into cells and have been widely used as carriers for intracellular delivery of bioactive molecules. In the early phase of the study, CPPs, as well as their conjugates, were thought to rapidly enter cells by direct penetration through membranes, which was later found to be an experimental artifact that was concluded from observatio

Extracellular vesicles (EVs) have attracted much attention as potential diagnostic biomarkers for human diseases. Although both plasma and serum are utilized as a source of blood EVs, it remains unclear whether, how and to what extent the choice of plasma and serum affects the experimental results. To address this issue, in this study, we performed comprehensive characterization of EV fractions derived from plasma and serum, and investigated the differences between these blood EVs. We demonstrat

T-cadherin is a unique cadherin cell adhesion molecule that is anchored to the cell surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. The cytoplasmic domain, which T-cadherin lacks, is believed to be critical for homophilic binding through interaction with submembrane cytoskeletal proteins. Does this mean that T-cadherin is an unimportant molecule? However, the T-cadherin amino acid motif has been well conserved through evolution in vertebrates, suggesting that T-cadherin m

The objective of this study was to introduce differential sensing techniques to synthetic systems that act, like olfactory receptors, as transporters in lipid bilayer membranes. Routine with most alternative chemosensing ensembles, pattern generation has, quite ironically, remained inaccessible in lipid bilayers because the number of available crossresponsive sensor components has been insufficient. To address this challenge, we here report on the use of cationic hydrazides that can react in sit

The polyglutamine (polyQ) diseases, such as Huntington's disease and several types of spinocerebellar ataxias, are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ tract in disease-causative proteins. Proteins with an abnormally expanded polyQ stretch undergo a conformational transition to β-sheet rich structure, which assemble into insoluble aggregates with β-sheet rich amyloid fibrillar structures and accumulate as inclusion bodies in neuron

We report that amphiphilic counterions can enable DNA to act as cation carrier, enzyme detector and biosensor. Calf thymus DNA is used as example throughout the study. Evaluation of a series of counterion activators suggests that strong amphiphilicity, alkyl or calix[4]arene tails and guanidinium cations give best results, whereas weak amphiphilicity, bola-amphiphilicity, planar aryl tails and ammonium cations are less satisfactory for various reasons. In the U-tube, DNA-counterion complexes can

This feature article offers a comprehensive account of a decade of research devoted to the combination of the grand sensing principles with synthetic transport systems that act in lipid bilayers. Differential sensing, that is pattern generation and pattern recognition, is exemplified with an artificial nose. The aptamer version of immunosensing is realized with sticky-end polymers of DNA double helices for both signal generation and signal transduction. Biosensing, that is the use of enzymes for

This chapter summarizes recent topics concerning the effect of amino acids and their derivatives, like taurine, peptides, tryptophan, lactoferrin, histamine, carnitine and thyroxine, on fish and shellfish.

We report that single-stranded (ss) DNA aptamers can be activated by counterions such as dodecylguanidinium (DG) to act as transporters in fluorogenic vesicles. However, their activity is independent of the presence or absence of the analyte. Dimerization into ds-DNA helices increases activity in an overadditive manner. Duplex disassembly in response to analyte binding is thus detectable as inactivation. Shortened and mismatched antiaptamers destabilize the active duplex, reduce activity, and in

The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although how TDP-43 forms cytoplasmic aggregates and causes neurodegeneration in patients with ALS/FTD remains unclear, reducing cellular TDP-43 levels is likely to prevent aggregation and to rescue neurons from TDP-43 toxicity. To address this issue, here we developed gapmer-type antisense oligonucleotides (ASOs)

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and polyglutamine diseases are caused by aggregation and abnormal accumulation of the disease-causative proteins in brain and spinal cord. Recent studies have suggested that proteins associated with neurodegenerative diseases are secreted and transmitted intercellularly via extracellular vesicles (EVs), which may be involved in propagation of abnormal protein accumulation and progressive de