SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found.

ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function.

Two new species of (Polyporales, Basidiomycota) in western China.

Two new species of , and , are described from western China. Phylogeny based on a six-gene dataset (ITS + nLSU + nSSU + mtSSU + TEF1 + RPB2) demonstrates that samples of the two species form two independent lineages within the clade of and are different in morphology from the existing species of . is characterized by its annual and resupinate basidiocarps with angular to irregular pores of 2-3 mm each and oblong ellipsoid to cylindrical basidiospores measuring 9-12 × 4.

HMGCS2-Induced Autophagic Degradation of Tau Involves Ketone Body and ANKRD24.

Background: Accumulation of hyperphosphorylated Tau (pTau) contributes to the formation of neurofibrillary tangles in Alzheimer's disease (AD), and targeting Tau/pTau metabolism has emerged as a therapeutic approach. We have previously reported that mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2 (HMGCS2) is involved in AD by promoting autophagic clearance of amyloid-β protein precursor via ketone body-associated mechanism, whether HMGCS2 may also regulate Tau metabolism remains elusive.

Objective: The present study was to investigate the role of HMGCS2 in Tau/p degradation.

Sulfuretin exerts diversified functions in the processing of amyloid precursor protein.

Sulfuretin is a flavonoid that protects cell from damage induced by reactive oxygen species and inflammation. In this study, we investigated the role of sulfuretin in the processing of amyloid precursor protein (APP), in association with the two catalytic enzymes the α-secretase a disintegrin and metalloproteinase (ADAM10), and the beta-site APP cleaving enzyme 1 (BACE1) that play important roles in the generation of β amyloid protein (Aβ) in Alzheimer's disease (AD). We found that sulfuretin increased the levels of the immature but not the mature form of ADAM10 protein.

TUFM is involved in Alzheimer's disease-like pathologies that are associated with ROS.

Mitochondrial Tu translation elongation factor (TUFM or EF-Tu) is part of the mitochondrial translation machinery. It is reported that TUFM expression is reduced in the brain of Alzheimer's disease (AD), suggesting that TUFM might play a role in the pathophysiology. In this study, we found that TUFM protein level was decreased in the hippocampus and cortex especially in the aged APP/PS1 mice, an animal model of AD.

[Effects of seed size and drought stress on the growth and physiological characteristics of seedlings].

The effects of seed size and drought stress on the growth and physiological characteristics of seedlings were investigated under shading conditions of a pot experiment in greenhouse. There were four treatments, including 80% field water content (FWC), 60% FWC, 40% FWC, and 20% FWC [CK, light drought stress (LDS), medium drought stress (MDS), and high drought stress (HDS), respectively]. The results showed that leaf area per plant, total dry mass, and root-shoot ratio of seedlings regenerated from large seeds (3.

Mitochondrial TXN2 attenuates amyloidogenesis via selective inhibition of BACE1 expression.

Thioredoxin-2 (TXN2) is a mitochondrial protein and represents one of the intrinsic antioxidant enzymes. It has long been recognized that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of Alzheimer's disease (AD). We hypothesized that mitochondrial TXN2 might play a role in AD-like pathology.

Age- and Nicotine-Associated Gene Expression Changes in the Hippocampus of APP/PS1 Mice.

The etiology of Alzheimer's disease (AD) has been intensively studied. However, little is known about the molecular alterations in early-stage and late-stage AD. Hence, we performed RNA sequencing and assessed differentially expressed genes (DEGs) in the hippocampus of 18-month and 7-month-old APP/PS1 mice.

Author Correction: Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer.

After publication of this article, it came to the attention of the authors that their names had been reordered. Professor. Jia Cao and Prof.

Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer.

Although TC2N has proven to be an oncogene in lung cancer, its biological function and molecular mechanisms in other cancer still remains unclear. Here, we investigate in breast cancer that TC2N expression is sharply overexpressed in breast cancer specimens compared with normal breast specimens, and the low TC2N expression was associated with advanced stage, lymphatic metastasis, larger tumors and shorter survival time. Upregulation of TC2N significantly restrains breast cancer cell proliferation in vitro and tumor growth in vivo.

Ubiquitination status does not affect Vps34 degradation.

Vps34 (vacuolar protein-sorting 34) plays important role in autophagy and endosomal trafficking. These processes are closely associated protein ubiquitination and degradation. We have hypothesized that Vps34 ubiquitination status would also control its degradation.

Mitochondrial methionine sulfoxide reductase B2 links oxidative stress to Alzheimer's disease-like pathology.

Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cell from oxidative stress. The antioxidant activity suggests that MSRB2 may play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, MSRB2 protein levels were decreased in the hippocampus at both young (6 mon) and old (18 mon) age, and in the cortex only at an old age, respectively.

Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice.

Cav1.2 is the pore-forming subunit of L-type voltage-gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective.

Functional characterization of short-type peptidoglycan recognition proteins (PGRPs) from silkworm Bombyx mori in innate immunity.

Peptidoglycan recognition proteins (PGRPs) are members of an important class of pattern recognition receptors in insects that can specifically recognize peptidoglycan (PGN) in bacterial cell walls and participate in immune regulation and bacterial clearance. Although the role of PGRPs in regulating the innate immune response in Drosophila melanogaster has been studied, little is known regarding PGRPs in Lepidoptera species. In this study, five short (S)-type Bombyx mori PGRPs (BmPGRPs) were cloned, expressed, and evaluated for their function in innate immunity.

MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation.

MMP13 (matrix metallopeptidase 13) plays a key role in bone metabolism and cancer development, but has no known functions in Alzheimer's disease. In this study, we used high-throughput small molecule screening in SH-SY5Y cells that stably expressed a luciferase reporter gene driven by the BACE1 (β-site amyloid precursor protein cleaving enzyme 1) promoter, which included a portion of the 5' untranslated region (5'UTR). We identified that CL82198, a selective inhibitor of MMP13, decreased BACE1 protein levels in cultured neuronal cells.

Pilomatricoma (calcifying epithelioma): MDCT and MR imaging findings in 31 patients with radiological-pathological correlation.

Purpose: To describe the radiological characteristics of pilomatricomas on multi-detector computed tomography (MDCT) and magnetic resonance imaging (MRI), and to correlate the radiological findings and pathological features.

Materials And Methods: The radiological findings of 41 pilomatricomas in 31 patients were retrospectively reviewed. The images were evaluated with emphasis on calcifications, reticular and ring-like appearances, enhancement patterns, circular target sign and peritumoral fat stranding, and correlating these with pathological features.

An ML protein from the silkworm Bombyx mori may function as a key accessory protein for lipopolysaccharide signaling.

Lipopolysaccharide (LPS) is a common component of the outermost cell wall in Gram-negative bacteria. In mammals, LPS serves as an endotoxin that can be recognized by a receptor complex of TLR4 (Toll-like receptor 4) and MD-2 (myeloid differentiation-2) and subsequently induce a strong immune response to signal the release of tumor necrosis factor (TNF). In Drosophila melanogaster, no receptors for LPS have been identified, and LPS cannot activate immune responses.

Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5'UTR and PI3K Signaling.

The α-secretase "a disintegrin and metalloproteinase domain-containing protein" (ADAM10) is involved in the processing of amyloid precursor protein (APP). Upregulation of ADAM10 precludes the generation of neurotoxic β-amyloid protein (Aβ) and represents a plausible therapeutic strategy for Alzheimer's disease (AD). In this study, we explored compounds that can potentially promote the expression of ADAM10.

Estrogen-related receptor alpha is involved in Alzheimer's disease-like pathology.

Estrogen-related receptor alpha (ERRα) is a transcriptional factor associated with mitochondrial biogenesis and energy metabolism. However, little is known about the role of ERRα in Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, ERRα protein and mRNA were decreased in a region- and age-dependent manner.

Phorbol esters dPPA/dPA promote furin expression involving transcription factor CEBPβ in neuronal cells.

Using high-throughput small molecule screening targeting furin gene, we identified that phorbol esters dPPA (12-Deoxyphorbol 13-phenylacetate 20-acetate) and dPA (12-Deoxyphorbol 13-acetate) significantly increased furin protein and mRNA expression in SH-SY5Y cells. This effect was prevented by PKC (protein kinase C) inhibitor calphostin C but not Ro318220, suggesting that the C1 domain, rather than the catalytic domain of PKC plays an important role. Luciferase assay revealed that nucleotides -7925 to -7426 were sufficient to mediate dPPA/dPA enhancement of P1 promoter activity.

BmCalpains are involved in autophagy and apoptosis during metamorphosis and after starvation in Bombyx mori.

Apoptosis and autophagy play crucial roles during Bombyx mori metamorphosis and in response to various adverse conditions, including starvation. Recently, calpain, one of the major intracellular proteases, has been reported to be involved in apoptosis and autophagy in mammals. BmATG5 and BmATG6 have been identified to mediate apoptosis following autophagy induced by 20-hydroxyecdysone and starvation in B.

Histone deacetylase inhibitor apicidin increases expression of the α-secretase ADAM10 through transcription factor USF1-mediated mechanisms.

ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) is the α-secretase that is involved in APP (β-amyloid precursor protein) processing. Enhancement of the nonamyloidogenic APP pathway by ADAM10 provides therapeutic potential for Alzheimer's disease (AD). By using high-throughput screening that targeted ADAM10, we determined that apicidin-an inhibitor of HDACs (histone deacetylases)-significantly increased mRNA and protein levels of ADAM10 in SH-SY5Y cells.

Plasma levels of soluble receptor for advanced glycation end products in Alzheimer's disease.

Background: A decreased plasma level of soluble form of the receptor for advanced glycation end products (sRAGE) in patients with Alzheimer's disease (AD) has been reported. However, no evidence has shown whether the sRAGE plasma level of AD patients may differentiate from other types of dementia.

Methods: Our study assessed sRAGE concentrations in the following 121 individuals in Chongqing area: 36 patients with AD, 12 with vascular dementia (VaD), 14 with mixed dementia (MD), 24 with other dementia (OD) including Parkinson's disease dementia, frontotemporal dementia, paralytic dementia and 35 cognitively normal controls.

Control of Drosophila blood cell activation via Toll signaling in the fat body.

The Toll signaling pathway, first discovered in Drosophila, has a well-established role in immune responses in insects as well as in mammals. In Drosophila, the Toll-dependent induction of antimicrobial peptide production has been intensely studied as a model for innate immune responses in general. Besides this humoral immune response, Toll signaling is also known to activate blood cells in a reaction that is similar to the cellular immune response to parasite infections, but the mechanisms of this response are poorly understood.