The microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer's disease. Although interaction with membranes is thought to affect some its physiological functions and aggregation properties, sequence determinants structural functional consequences such interactions remain poorly understood. Here, we report that vesicles results formation highly stable protein/phospholipid complexes. These complexes are toxic primary hippocampal cultures detected by MC-1, an...

Background: Alzheimer's disease (AD) is the major cause of dementia in population aged over 65 years, accounting up to 70% cases. However, validated peripheral biomarkers for AD diagnosis are not available present. In this study, we adopted a new strategy combination computational prediction and experimental validation identify blood protein AD. Methods: First, collected tissue-based gene expression data patients healthy controls from GEO database. Second, analyzed these identified...

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles regulating Tau's normal functions and its pathogenic properties tauopathies. Very little known about how phosphorylation tyrosine residues influences structure, aggregation, microtubule- lipid-binding Tau. Here, we sought to determine relative contributions one or...

Astrocytes, the most abundant glial cell type in brain, will convert into reactive state response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation astrocytes is partially attributed disruption autophagy lysosomal signaling, inhibiting some histone deacetylases (HDACs) has been demonstrated reduce molecular functional characteristics astrocytes. However, precise role signaling that regulates pathology...

The rational modification of protein stability is an important goal design. Protein surface electrostatic interactions are not evolutionarily optimized for and attractive target the redesign proteins. We show that charge mutants can exert stabilizing effects in distinct unanticipated ways, including ones predicted by existing methods, even when only solvent-exposed sites targeted. Individual mutation three lysines villin headpiece subdomain significantly stabilizes protein, but mechanism...

NMDA receptors are ligand-gated ion channels with a regulatory intracellular C-terminal domain (CTD). In GluN2B, the CTD is largest in protein but intrinsically disordered. The GluN2B subunit major tyrosine-phosphorylated synapses. Src kinase phosphorylates CTD, it unknown how this affects channel activity. disordered proteins, phosphorylation can tip balance between order and disorder. Transitions occur both directions, so not currently possible to predict effects of phosphorylation. We...

Understanding the folding of β-hairpin is a crucial step in studying how β-rich proteins fold. We have studied CLN025, an optimized ten residue synthetic peptide, which adopts compact, well-structured conformation. Formation component β-sheet and β-turn structures CLN025 was probed independently using combination equilibrium Fourier transform infrared spectroscopy laser-induced temperature jump coupled with time-resolved fluorescence spectroscopies. find that ultrafast folder due to its...

Xanthohumol is shown to interact with tau protein and inhibit its aggregation.

Polymannuronate (PM) is an acidic polysaccharide prepared from alginate, contained in edible brown seaweeds. An unsaturated mannuronate oligosaccharide (MOS) enzymatically depolymerized PM. The effects of MOS on attenuating tauopathy were studied HEK293/Tau cells and primary triple transgenic (3×Tg) neurons. inhibited heparin-induced aggregation the Tau-K18 oligomer suppressed levels phosphorylated Tau protein. treatment reduced activity glycogen synthase kinase-3β (GSK-3β) by decreasing its...

Alzheimer's disease (AD) is the most common type of dementia that occurs in elderly. Amyloid hypothesis one studied pathological mechanisms, and β-amyloid (Aβ) drug target for clinical trials. Mitochondrial dysfunction induced by Aβ-precursor protein (APP)/Aβ has been suggested to play a key role development AD. Here, we explored effects myricetin, polyphenol compound abundant fruits vegetables, on mitochondrial damages N2a-SW cells. After treatment depolarization was improved increasing...

The helical subdomain of the villin headpiece is smallest naturally occurring cooperatively folded protein. Its small size, simple three-helix topology, and very rapid folding have made it an extremely popular model system for computational theoretical studies protein folding. domain has a well-packed hydrophobic core comprised in part unusual set three closely packed phenylalanine residues, F47, F51, F58 (denoted using numbering larger protein). Aromatic−aromatic interactions been thought...

Abstract Alzheimer's disease (AD) is a serious neurodegenerative in people of age 65 or above. The detailed etiology and pathogenesis AD have not been elucidated yet. In this study, the hippocampi 2‐ 6‐month‐old triple transgenic male mice age–sex‐matched wild‐type (WT) were analyzed by using targeted metabolomics approach. Compared with WT mice, 24 60 metabolites found significant differences mice. Among these, 14 common while 10 showed consistent variable trends both groups. These...

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases without any effective medicine treatments. The neurofibrillary tangles containing hyperphosphorylated tau protein are important pathological characteristic. Thus, practicable strategy for AD drug design to discover compounds that could inhibit aggregation and/or phosphorylation. In this study, isobavachalcone, a natural plant-derived compound, has been shown and disaggregate fibrils in vitro by directly interacting...

The microtubule-associated protein tau can undergo liquid–liquid phase separation (LLPS) to form membraneless condensates in neurons, yet the underlying molecular mechanisms and functions of LLPS droplets remain be elucidated. human brain contains mainly 6 isoforms with different numbers microtubule-binding repeats (3R, 4R) N-terminal inserts (0N, 1N, 2N). However, little is known about role inserts. Here we observed dynamics three live neuronal cell line HT22. We validated cytoplasm found...

Alzheimer's disease (AD) is the most common age-related neurodegenerative threatening health of elderly, but available therapeutic and preventive drugs remain suboptimal. Loganin, an iridoid glycoside extracted from Cornus officinalis, reported to have anti-inflammatory memory-enhancing properties. This study aimed explore influence loganin on cognitive function in 3xTg-AD mice underlying mechanism associated with its neuroprotection. According results behavioral tests, we found that...

Small single domain proteins that fold on the microsecond time scale have been subject of intense interest as models for probing complexity folding energy landscapes. The villin headpiece subdomain (HP36) has extensively studied because its simple three helix structure, ultrafast lifetime a few microseconds, and stable native fold. We previously shown measured by 13C═18O isotopic label residue A57 in 2 occurs at different rate than global probes folding, indicating noncooperative HP36. In...

Intracellular tau accumulation is a hallmark pathology of Alzheimer's disease (AD) and other tauopathies. Tau protein, in the hyperphosphorylated form, component paired helical filaments (PHFs) neurofibrillary tangles (NFTs) AD. Blocking aggregation and/or phosphorylation currently promising strategy for AD treatment. Here, we elucidate that quercetagitrin, natural compound derived from African marigold (Tagetes erecta), could inhibit reduce at multiple disease-related sites vitro. Moreover,...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects 50 million people worldwide. The current medicines have modest benefits in preventing or curing AD. Thus, it urgent to discover drugs with the potential change progression of disease. primary clinical symptoms are memory loss and anxiety, while critical pathological characteristics Aβ plaques hyperphosphorylated tau tangles. In this study, isobavachalcone (ISO), isolated from Psoralea corylifolia, was...

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