Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD.

The GGGGCC hexanucleotide repeat expansion mutation in the chromosome 9 open reading frame 72 (C9orf72) gene is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). In this study, we demonstrate that the zinc finger (ZF) transcriptional regulator Yin Yang 1 (YY1) binds to the promoter region of the planar cell polarity gene Fuzzy to regulate its transcription. We show that YY1 interacts with GGGGCC repeat RNA via its ZF and that this interaction compromises the binding of YY1 to the Fuzzy promoter sites, resulting in the downregulation of Fuzzy transcription.

Application of lignin and lignin-based composites in different tissue engineering fields.

Lignin is a major phenolic polymer from the plant biomass. Due to its abundant functional groups (carboxyl and hydroxyl groups), lignin could act as an antioxidant, antimicrobial as well as an immune modulator. These remarkable biological properties render lignin a highly potential bioactive candidate in the biomedical applications including tissue engineering.

Lignin-carbohydrate complexes suppress SCA3 neurodegeneration via upregulating proteasomal activities.

Lignin-carbohydrate complexes (LCCs) represent a group of macromolecules with diverse biological functions such as antioxidative properties. Polyglutamine (polyQ) diseases such as spinocerebellar ataxia type 3 (SCA3) comprise a set of neurodegenerative disorders characterized by the formation of polyQ protein aggregates in patient neurons. LCCs have been reported to prevent such protein aggregation.

A peptide inhibitor that rescues polyglutamine-induced synaptic defects and cell death through suppressing RNA and protein toxicities.

Polyglutamine (polyQ) diseases, including spinocerebellar ataxias and Huntington's disease, are progressive neurodegenerative disorders caused by CAG triplet-repeat expansion in the coding regions of disease-associated genes. In this study, we found that neurotoxic small CAG (sCAG) RNA species, microscopic Ataxin-2 CAG RNA foci, and protein aggregates exist as independent entities in cells. Synaptic defects and neurite outgrowth abnormalities were observed in mutant Ataxin-2-expressing mouse primary cortical neurons.

Insight in the Recent Application of Polyphenols From Biomass.

Biomass polyphenols are bio-active macromolecules with distinct chemical structures in a variety of biomass. In recent years, the study of biomass polyphenols and their application in food and medicine fields has become a research hotspot, which predominantly focuses on the preparation, purification, structural identifications, and measurements of biological activities. Many studies describe methodologies for extraction and application of polyphenols, but comprehensive work to review its physiological activities like drugs and health products are lacking.

CAG RNAs induce DNA damage and apoptosis by silencing expression in polyglutamine degeneration.

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the () gene was down-regulated in mutant CAG RNA-expressing cells.

Pan-cancer investigation reveals mechanistic insights of planar cell polarity gene in carcinogenesis.

The fuzzy planar cell polarity protein (Fuz) is an effector component of the planar cell polarity (PCP) signaling. Together with other core and effector proteins, the PCP pathway controls polarized cell movements. Fuz was also reported as a negative regulator of cell survival.

A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report.

Background: CCDC88C is a ubiquitously expressed protein with multiple functions, including roles in cell polarity and the development of dendrites in the nervous system. Bi-allelic mutations in the CCDC88C gene cause autosomal recessive congenital hydrocephalus (OMIM #236600). Studies recently linked heterozygous mutations in CCDC88C to the development of the late-onset spinocerebellar ataxia type 40 (OMIM #616053).

A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3.

Polyglutamine (polyQ) diseases comprise Huntington's disease and several subtypes of spinocerebellar ataxia, including spinocerebellar ataxia type 3 (SCA3). The genomic expansion of coding CAG trinucleotide sequence in disease genes leads to the production and accumulation of misfolded polyQ domain-containing disease proteins, which cause cellular dysfunction and neuronal death. As one of the principal cellular protein clearance pathways, the activity of the ubiquitin-proteasome system (UPS) is tightly regulated to ensure efficient clearance of damaged and toxic proteins.

Isolation and Identification of a Novel Anti-protein Aggregation Activity of Lignin-Carbohydrate Complex From Leaves.

Lignin-carbohydrate complex (LCC) is the biological macromolecule that has been demonstrated to exert multiple biological functions, including antioxidant, anti-inflammation and anti-tumorigenesis, which support its broad application in the bioengineering field. However, it remains elusive the involvements of LCC in human neurological disorders, especially those with the overproduction of reactive oxygen species (ROS), such as spinocerebellar ataxias (SCAs). In this study, we found a previously undetermined anti-protein aggregation activity of LCC.

A Peptidylic Inhibitor for Neutralizing (GGGGCC)-Associated Neurodegeneration in C9ALS-FTD.

One drug, two diseases is a rare and economical therapeutic strategy that is highly desirable in the pharmaceutical industry. We previously reported a 21-amino acid peptide named beta-structured inhibitor for neurodegenerative diseases (BIND) that can effectively inhibit expanded CAG trinucleotide toxicity in polyglutamine (polyQ) diseases. Here we report that BIND also effectively inhibits GGGGCC repeat-mediated neurodegeneration in vitro and in vivo.

Transcriptional dysregulation in neurodegenerative diseases: Who tipped the balance of 1 in the brain?

Yin Yang 1 (YY1) is a multi-functional transcription factor that regulates gene expression in a range of cell types, including neurons. It controls neuronal differentiation, as well as neuronal specification and migration during the development of the mammalian nervous system. Besides, YY1 also mediates the transcription of genes that are required for neuronal survival.

FipoQ/FBXO33, a Cullin-1-based ubiquitin ligase complex component modulates ubiquitination and solubility of polyglutamine disease protein.

Polyglutamine (polyQ) diseases describe a group of progressive neurodegenerative disorders caused by the CAG triplet repeat expansion in the coding region of the disease genes. To date, nine such diseases, including spinocerebellar ataxia type 3 (SCA3), have been reported. The formation of SDS-insoluble protein aggregates in neurons causes cellular dysfunctions, such as impairment of the ubiquitin-proteasome system, and contributes to polyQ pathologies.

AQAMAN, a bisamidine-based inhibitor of toxic protein inclusions in neurons, ameliorates cytotoxicity in polyglutamine disease models.

Polyglutamine (polyQ) diseases are a group of dominantly inherited neurodegenerative disorders caused by the expansion of an unstable repeat in the coding region of the affected genes. Hallmarks of polyQ diseases include the accumulation of misfolded protein aggregates, leading to neuronal degeneration and cell death. PolyQ diseases are currently incurable, highlighting the urgent need for approaches that inhibit the formation of disaggregate cytotoxic polyQ protein inclusions.

Exo70 Is Essential for Neurite Extension and Survival under Thermal Stress.

The octomeric exocyst complex governs the final step of exocytosis in both plants and animals. Its roles, however, extend beyond exocytosis and include organelle biogenesis, ciliogenesis, cell migration, and cell growth. Exo70 is a conserved component of the exocyst whose function in is unclear.

Planar cell polarity gene triggers apoptosis in neurodegenerative disease models.

Planar cell polarity (PCP) describes a cell-cell communication process through which individual cells coordinate and align within the plane of a tissue. In this study, we show that overexpression of , a PCP gene, triggers neuronal apoptosis via the dishevelled/Rac1 GTPase/MEKK1/JNK/caspase signalling axis. Consistent with this finding, endogenous expression is upregulated in models of polyglutamine (polyQ) diseases and in fibroblasts from spinocerebellar ataxia type 3 (SCA3) patients.

A peptidylic inhibitor for neutralizing expanded RNA-induced nucleolar stress in polyglutamine diseases.

Polyglutamine (polyQ) diseases are a class of progressive neurodegenerative disorders characterized by the expression of both expanded RNA and misfolded polyQ protein. We previously reported that the direct interaction between expanded RNA and nucleolar protein nucleolin (NCL) impedes RNA () transcription, and eventually triggers nucleolar stress-induced apoptosis in polyQ diseases. Here, we report that a 21-amino acid peptide, named "beta-structured inhibitor for neurodegenerative diseases" (BIND), effectively suppresses toxicity induced by expanded RNA.