An 11-mer Synthetic Peptide Suppressing Aggregation of Aβ25-35 and Resolving Its Aggregated Form Improves Test Performance in an Aβ25-35-Induced Alzheimer's Mouse Model.

There is a high demand for the development of drugs against Alzheimer's disease (AD), which is related to the misfolding and aggregation of Amyloid-β (Aβ), due to the increasing number of patients with AD. In our present study, we aimed to assess the aggregation inhibitory effect of various synthetic YS-peptides on Aβ25-35 to identify an applicable peptide for clinical use for AD treatment and prevention. Suppression and aggregate resolution activities of YS-peptides against Aβ25-35 were evaluated using a Thioflavin T assay and scanning electron microscopy (SEM).

SKGQA, a Peptide Derived from the ANA/BTG3 Protein, Cleaves Amyloid-β with Proteolytic Activity.

Despite the extensive research conducted on Alzheimer's disease (AD) over the years, no effective drug for AD treatment has been found. Therefore, the development of new drugs for the treatment of AD is of the utmost importance. We recently reported the proteolytic activities of JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMA), synthetic peptides of nine amino acids each, derived from the Box A region of Tob1 and ANA/BTG3 proteins, respectively.

Five-mer peptides prevent short-term spatial memory deficits in Aβ25-35-induced Alzheimer's model mouse by suppressing Aβ25-35 aggregation and resolving its aggregate form.

Background: The development of drugs for Alzheimer's disease (AD), which is related to the misfolding and aggregation of amyloid-β (Aβ), is high in demand due to the growing number of AD patients. In this study, we screened 22 kinds of 5-mer synthetic peptides derived from the Box A region of Tob1 protein to find a peptide effective against Aβ aggregation.

Methods: A Thioflavin T (ThT) assay was performed to evaluate aggregation and screen aggregation inhibitors.

Structure-Activity Relationship of 5-mer Catalytides, GSGYR and RYGSG.

We recently discovered JAL-TA9 (YKGSGFRMI), a short hydrolytic peptide that we termed a Catalytide. The catalytic center of JAL-TA9 was modeled using MM2 and MMFF94 parameters and identified as GSGFR. Additionally, a structure-activity relationship study showed that GSGYR cleaved Aβ11-29.

Direct Delivery of ANA-TA9, a Peptide Capable of Aβ Hydrolysis, to the Brain by Intranasal Administration.

We have recently reported Catalytides (Catalytic peptides) JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMI), which are the first Catalytides found to cleave Aβ42. Although the Catalytides must be delivered to the brain parenchyma to treat Alzheimer's disease, the blood-brain barrier (BBB) limits their entry into the brain from the systemic circulation. To avoid the BBB, the direct route from the nasal cavity to the brain was used in this study.

Catalytides derived from the Box A region in the ANA/BTG3 protein cleave amyloid-β fragment peptide.

We have recently reported about shorter proteolytic peptides termed Catalytide as general name. JAL-TA9 (YKGSGFRMI), a fragment peptide derived from Box A region of Tob1 protein, is the first Catalytide and cleaves Aβ42 and its fragment peptides. Herein, we demonstrate the enzymatic properties of ANA-TA9 corresponding region to JAL-TA9 in ANA/BTG3 protein.

Effects of Cu on conformational change and aggregation of hPrP180-192 with a V180I mutation of the prion protein.

Prion diseases are neurodegenerative disorders caused by misfolding of the prion protein (PrP) from a normal cellular protein (PrP) to a protease-resistant isoform (PrP). However, the aggregation mechanism is not entirely understood because of the physical properties of PrP, such as its solubility or aggregation in vitro and conformational or mutation diversity. Recently, we reported the physical and physiological properties of a synthetic fragment peptide.

The discovery of shorter synthetic proteolytic peptides derived from Tob1 protein.

We screened nearly 1000 synthetic peptides and found that JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI), which is derived from the BoxA domain in the Tob1 protein, activates both unfolded and folded proMMP-7. Interestingly, the smaller derivative of JAL-AK22, termed JAL-TA9 (YKGSGFRMI) possessed auto-proteolytic activity and cleaved three synthetic peptides fragment (MMP18-33, MMP18-40, and Aβ11-29) under physiological conditions. The k of JAL-TA9 was 4.

MMP-7 cleaves amyloid β fragment peptides and copper ion inhibits the degradation.

The extracellular deposition of amyloid β (Aβ) is known to be the fundamental cause of Alzheimer's disease (AD). Aβ1-42, generated by β-secretases from the amyloid precursor protein (APP), is the main component of neuritic plaque, and the aggregation of this protein is shown to be dependent to an extent on metal ions such as copper and zinc. However, the mechanism by which Cu affects the physicochemical properties of Aβ1-42 or the central nervous system is still under debate.

Structure-activity relationship study at C9 position of kaitocephalin.

Kaitocephalin (KCP) isolated from Eupenicillium shearii PF1191 is an unusual amino acid natural product in which serine, proline, and alanine moieties are liked with carbon-carbon bonds. KCP exhibits potent and selective binding affinity for one of the ionotropic glutamate receptor subtypes, NMDA receptors (Ki=7.8nM).

(7S)-Kaitocephalin as a potent NMDA receptor selective ligand.

A structure-activity relationship (SAR) study of kaitocephalin (KCP), known to be a potent naturally occurring NMDA receptor ligand, was performed. This study led us to the discovery of (7S)-kaitocephalin as a highly selective NMDA receptor ligand. It displayed a 22-fold higher degree of selectivity for the NMDA receptor over KCP, though the binding affinity of (7S)-KCP [Ki = 29 nM] was 3.

[Studies Using Text Mining on the Differences in Learning Effects between the KJ and World Café Method as Learning Strategies].

The KJ method (named for developer Jiro Kawakita; also known as affinity diagramming) is widely used in participatory learning as a means to collect and organize information. In addition, the World Café (WC) has recently become popular. However, differences in the information obtained using each method have not been studied comprehensively.

[A self-improvement and participatory career development education program involving internships and volunteer training experience for pharmacy students: results verified in a follow-up survey three years after participation].

The Faculty of Pharmaceutical Sciences, Setsunan University, offers the Self-improvement and Participatory Career Development Education Program: Internship and Volunteer Training Experience for Pharmacy Students to third-year students. We previously reported that the training experience was effective in cultivating important attributes among students, such as a willingness to learn the aims of pharmacists, an awareness of their own role as healthcare workers, and a desire to reflect on their future careers and lives. A follow-up survey of the participants was carried out three years after the training experience.

[Practical chemistry education provided by team-based learning (TBL) and peer evaluation].

Learning chemistry is cumulative: basic knowledge and chemical calculation skills are required to gain understanding of higher content. However, we often suffer from students' lack of learning skills to acquire these concepts. One of the reasons is the lack of adequate training in the knowledge and skills of chemistry, and one of the reasons for this lack is the lack of adequate evaluation of training procedures and content.

Metal-binding ability of human prion protein fragment peptides analyzed by column switch HPLC.

The structural conversion of the prion protein (PrP) from the normal cellular isoform (PrP(C)) to the posttranslationally modified form (PrP(Sc)) is thought to relate to Cu²⁺ binding to histidine (H) residues. Traditionally, the binding of metals to PrP has been investigated by monitoring the conformational conversion using circular dichroism (CD). In this study, the metal-binding ability of 21 synthetic peptides representing regions of human PrP(C) was investigated by column switch high-performance liquid chromatography (CS-HPLC).

Novel digitalis-like factor, marinobufotoxin, isolated from cultured Y-1 cells, and its hypertensive effect in rats.

Marinobufagenin and telecinobufagin have been identified as digitalis-like factors in mammals. In toads, marinobufagenin-related compounds, such as marinobufotoxin (MBT), have been isolated in some tissues but not in mammals, and its biological action has not been elucidated. Herein, we aimed to explore the possible production and/or secretion of MBT and the biological action in rats.

Characterization of a novel metalloproteinase in Duvernoy's gland of Rhabdophis tigrinus tigrinus.

During the characterization of hemorrhagic factor in venom of Rhabdophis tigrinus tigrinus, so-called Yamakagashi in Japan, one of the Colubridae family, a novel metalloproteinase with molecular weight of 38 kDa in the Duvernoy's gland of Yamakagashi was identified by gelatin zymography and by monitoring its proteolytic activity using a fluorescence peptide substrate, MOCAc-PLGLA2pr(Dnp)AR-NH2, which was developed for measuring the well-known matrix metalloproteinase (MMP) activity. After purification by gel filtration HPLC and/or column switch HPLC system consisting of an affinity column, which was immobilized with a synthetic BS-10 peptide (MQKPRCGVPD) originating from propeptide domain of MMP-7 and a reversed-phase column, the N-terminal amino acid sequence of the 38 kDa metalloproteinase was identified as FNTFPGDLK which shared a high homology to Xenopus MMP-9. The 38 kDa metalloproteinase required Zn2+ and Ca2+ ions for its proteolytic activity.