How does the neuronal proteostasis network react to cellular cues?

Even though neurons are post-mitotic cells, they still engage in protein synthesis to uphold their cellular content balance, including for organelles, such as the endoplasmic reticulum or mitochondria. Additionally, they expend significant energy on tasks like neurotransmitter production and maintaining redox homeostasis. This cellular homeostasis is upheld through a delicate interplay between mRNA transcription-translation and protein degradative pathways, such as autophagy and proteasome degradation.

Disruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson's disease model.

Accumulation of advanced glycation end products (AGEs) on biopolymers accompanies cellular aging and drives poorly understood disease processes. Here, we studied how AGEs contribute to development of early onset Parkinson's Disease (PD) caused by loss-of-function of DJ1, a protein deglycase. In induced pluripotent stem cell (iPSC)-derived midbrain organoid models deficient for DJ1 activity, we find that lysosomal proteolysis is impaired, causing AGEs to accumulate, α-synuclein (α-syn) phosphorylation to increase, and proteins to aggregate.

The CRL3 ubiquitin ligase-USP15 pathway governs the destruction of neurofilament proteins.

Giant axonal neuropathy (GAN) is caused by mutations in the gene encoding for gigaxonin (GIG), which functions as an adaptor of the CUL3-RBX1-GIG (CRL3) E3 ubiquitin ligase complex. The pathological hallmark of GAN is characterized by the accumulation of densely packed neurofilaments (NFs) in the axons. However, there are fundamental knowledge gaps in our understanding of the molecular mechanisms by which the ubiquitin-proteasome system controls the homeostasis of NF proteins.

Quantitative proteome remodeling characterization of two human reference pluripotent stem cell lines during neurogenesis and cardiomyogenesis.

Human pluripotent stem cells (PSCs) have become popular tools within the research community to study developmental and model diseases. While many induced-PSCs (iPSCs) from various genetic background sources are currently available, scientific advancement has been hampered by the considerable phenotypic variations observed between different iPSC lines. A recent collaborative effort selected a novel iPSC line to address this and encourage the adoption of a standardized iPSC line termed KOLF2.

S6K1 controls adiponectin expression by inducing a transcriptional switch: BMAL1-to-EZH2.

Adiponectin (encoded by Adipoq), a fat-derived hormone, alleviates risk factors associated with metabolic disorders. Although many transcription factors are known to control adiponectin expression, the mechanism underlying its fluctuation with regard to metabolic status remains unclear. Here, we show that ribosomal protein S6 kinase 1 (S6K1) controls adiponectin expression by inducing a transcriptional switch between two transcriptional machineries, BMAL1 and EZH2.

Transcriptomics-Based Repositioning of Natural Compound, Eudesmin, as a PRC2 Modulator.

Extensive epigenetic remodeling occurs during the cell fate determination of stem cells. Previously, we discovered that eudesmin regulates lineage commitment of mesenchymal stem cells through the inhibition of signaling molecules. However, the epigenetic modulations upon eudesmin treatment in genomewide level have not been analyzed.

Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1.

Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with the anti-tumor effects of RAME in ovarian cancer.

Knockout of Gene ( Encoding bHLH Transcription Factor Using CRISPR/Cas9 System Confers Male Sterility Phenotype in Tomato.

The utilization of male sterility into hybrid seed production reduces its cost and ensures high purity of tomato varieties because it does not produce pollen and has exserted stigmas. Here, we report on the generation of gene edited lines into male sterility phenotype by knockout of gene ( encoding the bHLH transcription factor that regulates meiosis and cell death of the tapetum during microsporogenesis in the tomato. Twenty-eight gene edited lines out of 60 transgenic plants were selected.

Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus.

Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles.

In vitro modeling for inherited neurological diseases using induced pluripotent stem cells: from 2D to organoid.

Stem cells are characterized by self-renewal and by their ability to differentiate into cells of various organs. With massive progress in 2D and 3D cell culture techniques, in vitro generation of various types of such organoids from patient-derived stem cells is now possible. As in vitro differentiation protocols are usually made to resemble human developmental processes, organogenesis of patient-derived stem cells can provide key information regarding a range of developmental diseases.

Fermented ginseng extract, BST204, disturbs adipogenesis of mesenchymal stem cells through inhibition of S6 kinase 1 signaling.

Background: The biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway.

Ginsenoside Rg3 Induces Browning of 3T3-L1 Adipocytes by Activating AMPK Signaling.

Ginsenoside Rg3, one of the major components in , has been reported to possess several therapeutic effects including anti-obesity properties. However, its effect on the browning of mature white adipocytes as well as the underlying mechanism remains poorly understood. In this study, we suggested a novel role of Rg3 in the browning of mature 3T3-L1 adipocytes by upregulating browning-related gene expression.

(±)-Kituramides A and B, pairs of enantiomeric dopamine dimers from the two-spotted cricket Gryllus bimaculatus.

Two-spotted cricket Gryllus bimaculatus is one of many cricket species, and it is widely used as a food source for insectivorous animals. Moreover, this species is one of the edible insects approved by the Korea Food and Drug Administration (KFDA). (±)-Kituramides A (1) and B (2), which are pairs of novel enantiomeric dopamine dimers possessing a formamide group, were isolated from the two-spotted cricket, together with four other known biosynthetically related compounds (3-6).

Vulpinic Acid Controls Stem Cell Fate toward Osteogenesis and Adipogenesis.

Vulpinic acid, a naturally occurring methyl ester of pulvinic acid, has been reported to exert anti-fungal, anti-cancer, and anti-oxidative effects. However, its metabolic action has not been implicated yet. Here, we show that vulpinic acid derived from a mushroom, controls the cell fate of mesenchymal stem cells and preadipocytes by inducing the acetylation of histone H3 and α-tubulin, respectively.

Anti-adipogenic Effect of β-Carboline Alkaloids from Garlic ().

Garlic ( L.) is utilized worldwide for culinary and medicinal use and has diverse health benefits. As part of our ongoing research to identify bioactive components from natural resources, phytochemical analysis of the methanolic extract of garlic led to the isolation and characterization of six compounds: Three eugenol diglycosides (-) and three β-carboline alkaloids (-).

Pantheric Acids A-C from a Poisonous Mushroom, , Promote Lipid Accumulation in Adipocytes.

is a poisonous mushroom that causes muscle cramps, insanity, and audiovisual disorders. As part of our systematic study on Korean mushrooms, a chemical investigation of fruiting bodies resulted in the isolation and structural identification of three new fatty acid derivatives, pantheric acids A-C (-), and a known compound, 1,10-dimethyl ester-2-decenedioic acid (). Although 1,10-dimethyl ester-2-decenedioic acid () was previously reported as a synthetic product, it was structurally identified from a natural source for the first time.

Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer.

Background: The mTOR/S6K1 signaling pathway is often activated in cervical cancer, and thus considered a molecular target for cervical cancer therapies. Inhibiting mTOR is cytotoxic to cervical cancer cells and creates a synergistic anti-tumor effect with conventional chemotherapy agents. In this study, we identified a novel S6K1 inhibitor, rosmarinic acid methyl ester (RAME) for the use of therapeutic agent against cervical cancer.

Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway.

Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin disturbs adipogenesis via suppression of S6K1 signaling pathway.

Reversine promotes browning of white adipocytes by suppressing miR-133a.

Brown adipocytes are characterized by a high number of uncoupling protein 1 (UCP1)-positive mitochondrial content and increased thermogenic capacity. As UCP1-enriched cells can consume lipids by generating heat, browning of white adipocytes is now highlighted as a promising approach for the prevention of obesity and obesity-associated metabolic diseases. Upon cold exposure or β-adrenergic stimuli, downregulation of microRNA-133 (miR-133) elevates the expression levels of PR domain containing 16 (Prdm16), which has been shown to be a brown adipose determination factor, in brown adipose tissue and subcutaneous white adipose tissues (WAT).