Complement 3a induces the synapse loss via C3aR in mitochondria-dependent NLRP3 activating mechanisms during the development and progression of Alzheimer's disease.

As a central molecule in complement system (CS), complement (C) 3 is upregulated in the patients and animal models of Alzheimer's disease (AD). C3 will metabolize to iC3b and C3a. iC3b is responsible for clearing β-amyloid protein (Aβ).

As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease.

C1q, the initiator of the classical pathway of the complement system, is activated during Alzheimer's disease (AD) development and progression and is especially associated with the production and deposition of β-amyloid protein (Aβ) and phosphorylated tau in β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Activation of C1q is responsible for induction of synapse loss, leading to neurodegeneration in AD. Mechanistically, C1q could activate glial cells, which results in the loss of synapses via regulation of synapse pruning and phagocytosis in AD.

The Involvement of Post-Translational Modifications in Regulating the Development and Progression of Alzheimer's Disease.

Post-translational modifications (PTMs) have been recently reported to be involved in the development and progression of Alzheimer's disease (AD). In detail, PTMs include phosphorylation, glycation, acetylation, sumoylation, ubiquitination, methylation, nitration, and truncation, which are associated with pathological functions of AD-related proteins, such as β-amyloid (Aβ), β-site APP-cleavage enzyme 1 (BACE1), and tau protein. In particular, the roles of aberrant PTMs in the trafficking, cleavage, and degradation of AD-associated proteins, leading to the cognitive decline of the disease, are summarized under AD conditions.

Molecular mechanism of acetylsalicylic acid in improving learning and memory impairment in APP/PS1 transgenic mice by inhibiting the abnormal cell cycle re-entry of neurons.

Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by the loss and apoptosis of neurons. Neurons abnormally enter the cell cycle, which results in neuronal apoptosis during the course of AD development and progression. However, the mechanisms underlying cell cycle re-entry have been poorly studied.

Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the production and deposition of β-amyloid protein (Aβ) and hyperphosphorylated tau, leading to the formation of β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Although calcium ions (Ca) promote the formation of APs and NFTs, no systematic review of the mechanisms by which Ca affects the development and progression of AD has been published. Therefore, the current review aimed to fill the gaps between elevated Ca levels and the pathogenesis of AD.

Downregulating expression of OPTN elevates neuroinflammation via AIM2 inflammasome- and RIPK1-activating mechanisms in APP/PS1 transgenic mice.

Background: Neuroinflammation is thought to be a cause of Alzheimer's disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD.

Methods: BV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD.

Indomethacin Disrupts the Formation of β-Amyloid Plaques via an α2-Macroglobulin-Activating lrp1-Dependent Mechanism.

Epidemiological studies have implied that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the development and progression of Alzheimer's disease (AD). However, the underlying mechanisms are notably understudied. Using a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) (APP/PS1) expressing transgenic (Tg) mice and neuroblastoma (N) 2a cells as in vivo and in vitro models, we revealed the mechanisms of indomethacin in ameliorating the cognitive decline of AD.

Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau.

Alzheimer's disease (AD) is a neurodegenerative disease with a high incidence rate. The main pathological features of AD are β-amyloid plaques (APs), which are formed by β-amyloid protein (Aβ) deposition, and neurofibrillary tangles (NFTs), which are formed by the excessive phosphorylation of the tau protein. Although a series of studies have shown that the accumulation of metal ions, including calcium ions (Ca), can promote the formation of APs and NFTs, there is no systematic review of the mechanisms by which Ca affects the development and progression of AD.

New phenolic glycosides from Bunge and their antioxidant activity.

ABATRACTNine compounds, five phenolic glycosides (, , ), three phenylpropanoids (), and a furanone glycoside (), were isolated from aqueous soluble extract of the dried roots of Bunge. The structures of new compounds () were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A () demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.

Prostaglandin A1 Decreases the Phosphorylation of Tau by Activating Protein Phosphatase 2A via a Michael Addition Mechanism at Cysteine 377.

Prostaglandin (PG) A1 is a metabolic product of cyclooxygenase 2 (COX-2) that is potentially involved in regulating the development and progression of Alzheimer's disease (AD). PGA1 is a cyclopentenone (cy) PG characterized by the presence of a chemically reactive α,β-unsaturated carbonyl. PGA1 is potentially involved in the regulation of multiple biological processes via Michael addition; however, the specific roles of PGA1 in AD remain unclear.

Cyclooxygenase-2 Induced the β-Amyloid Protein Deposition and Neuronal Apoptosis Via Upregulating the Synthesis of Prostaglandin E and 15-Deoxy-Δ-prostaglandin J.

Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) have been shown to be involved in the pathogenesis of Alzheimer's disease. Analysis of the underlying mechanisms elucidated a function of sequential PGE and PGD synthesis in regulating β-amyloid protein (Aβ) deposition by modulating tumor necrosis factor α (TNF-α)-dependent presenilin (PS)1/2 activity in COX-2 and APP/PS1 crossed mice. Specifically, COX-2 overexpression accelerates the expression of microsomal PGE synthase-1 (mPGES-1) and lipocalin-type prostaglandin D synthase (L-PGDS), leading to the synthesis of PGE and 15-deoxy-Δ-prostaglandin J (15d-PGJ) in 6-month-old APP/PS1 mice.

Calcium Ions Stimulate the Hyperphosphorylation of Tau by Activating Microsomal Prostaglandin E Synthase 1.

Alzheimer's disease (AD) is reportedly associated with the accumulation of calcium ions (Ca), and this accumulation is responsible for the phosphorylation of tau. Although several lines of evidence demonstrate the above phenomenon, the inherent mechanisms remain unknown. Using APP/PS1 Tg mice and neuroblastoma (N)2a cells as and experimental models, we observed that Ca stimulated the phosphorylation of tau by activating microsomal PGE synthase 1 (mPGES1) in a prostaglandin (PG) E-dependent EP receptor-activating manner.

Cyclooxygenase-2 is Essential for Mediating the Effects of Calcium Ions on Stimulating Phosphorylation of Tau at the Sites of Ser 396 and Ser 404.

Alzheimer's disease (AD) is reported to be associated with the accumulation of calcium ions (Ca2+), which is responsible for the phosphorylation of tau. Although a series of evidence have demonstrated this phenomenon, the inherent mechanisms remain unknown. Using tauP301S and cyclooxygenase-2 (COX-2) transgenic mice and neuroblastoma (n)2a cells as in vivo and in vitro experimental models, we found that Ca2+ stimulates the phosphorylation of tau by activating COX-2 in a prostaglandin (PG) E2-dependent EP receptor-activating manner.

Prostaglandin A1 Inhibits the Cognitive Decline of APP/PS1 Transgenic Mice via PPARγ/ABCA1-dependent Cholesterol Efflux Mechanisms.

Prostaglandins (PGs) are early and key contributors to chronic neurodegenerative diseases. As one important member of classical PGs, PGA1 has been reported to exert potential neuroprotective effects. However, the mechanisms remain unknown.

The roles of prostaglandin F in regulating the expression of matrix metalloproteinase-12 via an insulin growth factor-2-dependent mechanism in sheared chondrocytes.

Osteoarthritis (OA) was recently identified as being regulated by the induction of cyclooxygenase-2 (COX-2) in response to high fluid shear stress. Although the metabolic products of COX-2, including prostaglandin (PG)E, 15-deoxy-Δ-PGJ (15d-PGJ), and PGF, have been reported to be effective in regulating the occurrence and development of OA by activating matrix metalloproteinases (MMPs), the roles of PGF in OA are largely overlooked. Thus, we showed that high fluid shear stress induced the mRNA expression of MMP-12 via cyclic (c)AMP- and PGF-dependent signaling pathways.

Transferrin is responsible for mediating the effects of iron ions on the regulation of anterior pharynx-defective-1α/β and Presenilin 1 expression via PGE and PGD at the early stage of Alzheimer's Disease.

Transferrin (Tf) is an important iron-binding protein postulated to play a key role in iron ion (Fe) absorption via the Tf receptor (TfR), which potentially contributes to the pathogenesis of Alzheimer's disease (AD). However, the role of Tf in AD remains unknown. Using mouse-derived neurons and APP/PS1 transgenic (Tg) mice as model systems, we firstly revealed the mechanisms of APH-1α/1β and presenilin 1 (PS1) upregulation by Fe in prostaglandin (PG) E- and PGD-dependent mechanisms.

Integrated communications between cyclooxygenase-2 and Alzheimer's disease.

Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) are involved in the pathogenesis of Alzheimer's disease (AD), which is characterized by the accumulation of β-amyloid protein (Aβ) and tau hyperphosphorylation. However, the gaps in our knowledge of the roles of COX-2 and PGs in AD have not been filled. Here, we summarized the literature showing that COX-2 dysregulation obviously influences abnormal cleavage of β-amyloid precursor protein, aggregation and deposition of Aβ in β-amyloid plaques and the inclusion of phosphorylated tau in neurofibrillary tangles.

Magnesium Ions Inhibit the Expression of Tumor Necrosis Factor α and the Activity of γ-Secretase in a β-Amyloid Protein-Dependent Mechanism in APP/PS1 Transgenic Mice.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. The neuropathological features of AD are the aggregation of extracellular amyloid β-protein (Aβ) and tau phosphorylation. Recently, AD was found to be associated with magnesium ion (Mg) deficit and tumor necrosis factor-alpha (TNF-α) elevation in the serum or brains of AD patients.

COX-2 metabolic products, the prostaglandin I and F, mediate the effects of TNF-α and Zn in stimulating the phosphorylation of Tau.

Although the roles of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) in regulating amyloid precursor protein (APP) cleavage and β-amyloid protein (Aβ) production have been the subjects of numerous investigations, their effects on tau phosphorylation have been largely overlooked. Using human Tau transgenic (Tg) mice as model, our results demonstrated that PGI and PGF mediated the effects of tumor necrosis factor α (TNF-α) and Zinc ions (Zn) on upregulating the phosphorylation of tau via the PI3-K/AKT, ERK1/2 and JNK/c-Jun signaling pathways. Specifically, we initially found that high level of Zn upregulates the expression of COX-2 via stimulating the activity of TNF-α in a zinc transporter 3 (ZnT3)-dependent mechanism.

New Iridoids from Scrophularia ningpoensis.

Five new compounds including five iridoids (1-5) and six known compounds were isolated from the rhizomes of Scrophularia ningpoensis. Their structures were determined by extensive NMR and IR, MS spectroscopic data analyses. The anti-inflammatory, antibacterial, antifungal, and cytotoxic activities of the isolated compounds were evaluated.

Erythrocyte membrane-encapsulated celecoxib improves the cognitive decline of Alzheimer's disease by concurrently inducing neurogenesis and reducing apoptosis in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is characterized by the loss of neurogenesis and excessive induction of apoptosis. The induction of neurogenesis and inhibition of apoptosis may be a promising therapeutic approach to combating the disease. Celecoxib (CB), a cyclooxygenase-2 specific inhibitor, could offer neuroprotection.

[Genetic Polymorphism of HPA 1-17 Alloantigen System in Heilongjiang Menggu Population].

Objective: To explore the polymorphisms of the human platelet antigen (HPA) gene of Han and Menggu population of Heilongjiang province in China, to determine platelet antigen system with clinical significance by judging the rate of incompatibility of HPA, as well as to establish a database of donors HPA including the Han nationality and the minority nationality.

Methods: The samples of unrelated healthy Menggu population (100 cases) people were selected from Heilongjiang province in China, and 123 cases in healthy Han population in Heilongjiang as control were collected. The technique of PCR-sequence specific primers (PCR-SSP) was used for genotyping of 34 alleles in HPA1-17 gene.