Charge Modification of Lysine Mitigates Amyloid-β Aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by the deposition of amyloid-β (Aβ) peptides, which aggregate into toxic structures such as oligomers, fibrils, and plaques. The presence of these Aβ aggregates in the brain plays a crucial role in the pathophysiology, leading to synaptic dysfunction and cognitive impairment. Understanding how physiological factors affect Aβ aggregation is essential, and therefore, exploring their influence in vitro will likely provide insights into their role in AD pathology.

Modulation of Amyloid and Tau Aggregation to Alleviate Cognitive Impairment in a Transgenic Mouse Model of Alzheimer's Disease.

Aggregation of misfolded amyloid-β (Aβ) and hyperphosphorylated tau proteins to plaques and tangles, respectively, is the major drug target of Alzheimer's disease (AD), as the former is an onset biomarker and the latter is associated with neurodegeneration. Thus, we report a small molecule drug candidate, DN5355, with a dual-targeting function toward aggregates of both Aβ and tau. DN5355 was selected through a series of four screenings assessing 52 chemicals for their functions to inhibit and reverse the aggregation of Aβ and tau by utilizing thioflavin T.

Early onset diagnosis in Alzheimer's disease patients via amyloid-β oligomers-sensing probe in cerebrospinal fluid.

Amyloid-β (Aβ) oligomers are implicated in the onset of Alzheimer's disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB) fluorescent probe was designed for detecting Aβ oligomers by finely tailoring the hydrophobicity of the biannulate donor motifs in donor-π-acceptor structure. Q-OB shows a great sensing potency in dynamically monitoring oligomerization of Aβ during amyloid fibrillogenesis in vitro.

Benzo[]imidazole-pyrrolo[1,2-]pyrazine Hybrids Ameliorate Amyloid Aggregates in the Brain of Alzheimer Transgenic Mice.

Abnormal assembly of amyloid β (Aβ) in the brain is implicated in Alzheimer's disease (AD) and is associated with cognitive impairments. Since Aβ accumulation occurs in advance of the onset of clinical symptoms, identifying preventable drug candidates regulating Aβ accumulation is regarded as a promising approach in AD therapeutic. Herein, we synthesized eight Yonsei Institute of pharmaceutical sciences Alzheimer's Drug (YIAD) compounds based on 5-benzyl-6-phenylbenzo[4,5]imidazo[1,2-]pyrrolo[2,1-]pyrazine structures.

4-Acyl-3,4-dihydropyrrolo[1,2-]pyrazine Derivative Rescued the Hippocampal-Dependent Cognitive Decline of 5XFAD Transgenic Mice by Dissociating Soluble and Insoluble Aβ Aggregates.

Cerebral amyloid-β (Aβ) deposition is a representative hallmark of Alzheimer's disease (AD). Development of Aβ-clearing small molecules could be an advantageous therapeutic strategy for Aβ clearance considering the advantages in terms of side effects, cost-effectiveness, stability, and oral bioavailability. Here, we report an Aβ-dissociating small molecule, YIAD-0121, a derivative of 4-acyl-3,4-dihydropyrrolo[1,2-]pyrazine.

Solid-phase synthesis and pathological evaluation of pyroglutamate amyloid-β peptide.

Pyroglutamate amyloid-β (Aβ) is an N-terminally truncated and pyroglutamate-modified Aβ peptide retaining highly hydrophobic, amyloidogenic, and neurotoxic properties. In Alzheimer's disease (AD) patients, Aβ peptides accumulate into oligomers and induce cellular toxicity and synaptic dysfunction. Aβ aggregates further seed the formation of amyloid plaques, which are the pathological hallmarks of AD.

A Therapeutic Nanovaccine that Generates Anti-Amyloid Antibodies and Amyloid-specific Regulatory T Cells for Alzheimer's Disease.

Alzheimer's disease (AD), the most common cause of dementia, is a complex condition characterized by multiple pathophysiological mechanisms including amyloid-β (Aβ) plaque accumulation and neuroinflammation in the brain. The current immunotherapy approaches, such as anti-Aβ monoclonal antibody (mAb) therapy, Aβ vaccines, and adoptive regulatory T (Treg) cell transfer, target a single pathophysiological mechanism, which may lead to unsatisfactory therapeutic efficacy. Furthermore, Aβ vaccines often induce T helper 1 (Th1) cell-mediated inflammatory responses.

Amyloid Against Amyloid: Dimeric Amyloid Fragment Ameliorates Cognitive Impairments by Direct Clearance of Oligomers and Plaques.

Amyloid-β (Aβ) in the form of neurotoxic aggregates is regarded as the main pathological initiator and key therapeutic target of Alzheimer's disease. However, anti-Aβ drug development has been impeded by the lack of a target needed for structure-based drug design and low permeability of the blood-brain barrier (BBB). An attractive therapeutic strategy is the development of amyloid-based anti-Aβ peptidomimetics that exploit the self-assembling nature of Aβ and penetrate the BBB.

Quinacrine directly dissociates amyloid plaques in the brain of 5XFAD transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia characterized by the abnormal accumulation of amyloid-β (Aβ) in the brain. Aβ misfolding is associated with neuroinflammation and synaptic dysfunction, leading to learning and memory deficits. Therefore, Aβ production and aggregation have been one of the most popular drug targets for AD.

Azetidine-Bearing Non-Ribosomal Peptides, Bonnevillamides D and E, Isolated from a Carrion Beetle-Associated Actinomycete.

Two new nonribosomal peptides, bonnevillamides D and E ( and ), have been discovered in sp. UTZ13 isolated from the carrion beetle, . Combinational analysis of the UV, MS, and NMR spectroscopic data revealed that their planar structures were comprised of dichlorinated linear peptides containing nonproteinogenic amino acid residues, such as 4-methylazetidinecarboxylic acid and 4--acetyl-5-methylproline.

High Temperature Oxidation Behavior of Cr-Al-Si-N Nanocomposite Films Deposited by Filtered Arc Ion Plating Technique.

High temperature oxidation behavior of nanocomposite films is very important characteristics for application of machining and cutting tools. Quaternary Cr-Al-Si-N nanocomposite films with various compositions were deposited onto WC-Co and Si wafer substrates using a filtered arc ion plating technique. The composition of the films were controlled by different combinations of CrAl₂ and Cr₄Si composite target power in a reactive gas mixture of high purity Ar and N₂ during depositions.

Multi-Functional Cr-Al-Ti-Si-N Nanocomposite Films Deposited on WC-Co Substrate for Cutting Tools.

Multi-functional quinary Cr-Al-Ti-Si-N thin films were deposited onto WC-Co substrates using a cathodic arc evaporation system. In this study, the influence of silicon contents on the microstructure, mechanical, tribological, and oxidation properties of Cr-Al-Ti-Si-N thin films were systematically investigated and correlated for application of cutting tools. Based on results from various analyses, the Cr-Al-Ti-Si-N films showed excellent properties including mechanical, tribological, oxidation and adhesion values compared with those of the Cr-Al-Ti-N film.

Effect of Vanadium Addition on the High-Temperature Friction Behavior in Nanostructured Al-Cr-V-N Films Prepared by UBMS.

In recent year, vanadium-doped tribological films have become available as possible candidates for self-lubrication at high temperatures. In this work, quaternary Al-Cr-V-N films were deposited onto silicon wafer and WC-Co substrates by an unbalanced magnetron sputtering using high purity (99.99%) CrAl₂ and V targets with argon-nitrogen reactive gases.

Oxidation Behavior of Ti-Al-Si-N-O Nanocomposite Films Deposited by Filtered Arc Ion Plating Technique.

Oxidation behavior of nanocomposite films is very important characteristics for application of machining and cutting tools. In this study, Ti-Al-Si-N-O nanocomposite films were fabricated onto WC-Co and Si wafer substrates. The composition of the Ti-Al-Si-N-O films was analyzed by X-ray photo-electron spectroscope (XPS).

Microstructure and Mechanical Properties of Functional Graded Ti-Al-Si-N-O Nanocomposite Films Deposited by Filtered Arc Ion Plating Technique.

Functional graded Ti-Al-Si-N-O nanocomposite films were deposited onto WC-Co substrate by a filtered arc ion plating system using TiAl and TiSi composite targets under N₂/Ar atmosphere. XRD and XPS analyses revealed that the synthesized Ti-Al-Si-N-O films were nanocomposite consisting of nanosized (Ti, Al, Si)N crystallites embedded in an amorphous Si₃N₄/SiO₂ matrix. The hardness of the Ti-Al-Si-N-O films exhibited the maximum hardness values of ~47 GPa at a Si content of ~5.

Oxidation and Tribological Behavior of Ti-B-C-N-Si Nanocomposite Films Deposited by Pulsed Unbalanced Magnetron Sputtering.

Quinary Ti-B-C-N-Si nanocomposite films were deposited onto AISI 304 substrates using a pulsed d.c. magnetron sputtering system.

Processing, structure, and properties of nanostructured multifunctional tribological coatings.

Nanostructured, nanocomposite binary (TiC-a:C), ternary (Cr-Al-N), quaternary (Ti-B-C-N) and quinternary (Ti-Si-B-C-N) multicomponent films have been deposited using unbalanced magnetron sputtering (UBMS) and closed field unbalanced magnetron sputtering (CFUBMS) from both elemental and composite targets. Approaches to control the film chemistry, volume fraction and size of the multicomponent species, and pulsed ion energy (ion flux) bombardment to tailor the structure and properties of the films for specific tribological applications, e.g.