CGN

Last update 08 May 2025

Basic Info

Synonyms

CGN, cingulin, KIAA1319

Introduction

Probably plays a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.

100 Clinical Results associated with CGN

100 Translational Medicine associated with CGN

0 Patents (Medical) associated with CGN

263

Literatures (Medical) associated with CGN

06 Jan 2025·Molecular Pharmaceutics

Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2 In Vitro and In Vivo in Mice

Article

Author: Singh, Jagdish ; Gothwal, Avinash ; Muolokwu, Chinenye Edith ; Kanekiyo, Takahisa

Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by the aggregation of amyloid-β plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and neuronal degeneration. Recently, new treatment approaches involving drugs such as donanemab and lecanemab have been introduced for AD. However, these drug regimens have been associated with adverse effects, leading to the exploration of gene therapy as a potential treatment option. The apolipoprotein E (ApoE) isoforms (ApoE2, ApoE3, and ApoE4) play pivotal roles in AD pathology, with ApoE2 known for its protective effects against AD, making it a promising candidate for gene therapy interventions. However, delivering therapeutics across the blood-brain barrier (BBB) remains a crucial challenge in treating neurological disorders. Liposomes, lipid-based vesicles, are effective nanocarriers due to their ability to shield therapeutics from degradation, though they often lack specificity for brain delivery. To address this issue, liposomes were functionalized with cell-penetrating peptides such as penetratin (Pen), cingulin (Cgn), and a targeting ligand transferrin (T_f). This modification strategy aimed to enhance the delivery of therapeutic ApoE2 plasmids across the BBB to neurons, thereby increasing the level of ApoE2 protein expression. Experimental findings demonstrated that dual-functionalized liposomes (CgnT_f and PenT_f) exhibited higher cellular uptake, biodistribution, and transfection efficiency than single-functionalized (Pen, Cgn, or T_f) and nonfunctionalized liposomes. In vitro studies using primary neuronal cells, bEnd.3 cells, and primary astrocytes consistently supported these findings. Following a single dose treatment via tail vein administration in C57BL6/J mice, in vivo biodistribution results showed significantly higher biodistribution levels in the brain (∼12% ID/gram of tissue) for dual-functionalized liposomes. Notably, treatment with dual-functionalized liposomes resulted in a 2-fold increase in ApoE2 expression levels compared to baseline levels. These findings highlight the potential of dual-functionalized liposomes as an efficacious delivery system for ApoE2 gene therapy in AD, highlighting a promising strategy to address the disease's underlying mechanisms.

06 Nov 2024·G3: Genes, Genomes, Genetics

Genomic factors shaping codon usage across the Saccharomycotina subphylum

Article

Author: Shen, Xing-Xing ; Fisher, Kaitlin J ; Wolters, John F ; Zavala, Bryan ; Groenewald, Marizeth ; Hittinger, Chris Todd ; Opulente, Dana A ; Rokas, Antonis ; Dineen, Lauren ; LaBella, Abigail Leavitt ; Zhou, Xiaofan ; Harrison, Marie-Claire

AbstractCodon usage bias, or the unequal use of synonymous codons, is observed across genes, genomes, and between species. It has been implicated in many cellular functions, such as translation dynamics and transcript stability, but can also be shaped by neutral forces. We characterized codon usage across 1,154 strains from 1,051 species from the fungal subphylum Saccharomycotina to gain insight into the biases, molecular mechanisms, evolution, and genomic features contributing to codon usage patterns. We found a general preference for A/T-ending codons and correlations between codon usage bias, GC content, and tRNA-ome size. Codon usage bias is distinct between the 12 orders to such a degree that yeasts can be classified with an accuracy >90% using a machine learning algorithm. We also characterized the degree to which codon usage bias is impacted by translational selection. We found it was influenced by a combination of features, including the number of coding sequences, BUSCO count, and genome length. Our analysis also revealed an extreme bias in codon usage in the Saccharomycodales associated with a lack of predicted arginine tRNAs that decode CGN codons, leaving only the AGN codons to encode arginine. Analysis of Saccharomycodales gene expression, tRNA sequences, and codon evolution suggests that avoidance of the CGN codons is associated with a decline in arginine tRNA function. Consistent with previous findings, codon usage bias within the Saccharomycotina is shaped by genomic features and GC bias. However, we find cases of extreme codon usage preference and avoidance along yeast lineages, suggesting additional forces may be shaping the evolution of specific codons.

01 Nov 2024·Journal of Genetics and Genomics

A human-specific cytotoxic neopeptide generated by the deafness gene Cingulin

Article

Author: Gao, Xia ; Chen, Jie ; Zhu, Guang-Jie ; Qian, Xiaoyun ; Huang, Yuhang ; Wan, Guoqiang ; Zhang, Linqing ; Sun, Yuecen ; Liu, Qing

Accumulation of mutant proteins in cells can induce proteinopathies and cause functional damage to organs. Recently, the Cingulin (CGN) protein has been shown to maintain the morphology of cuticular plates of inner ear hair cells and a frameshift mutation in CGN causes autosomal dominant non-syndromic hearing loss. Here, we find that the mutant CGN proteins form insoluble aggregates which accumulate intracellularly and lead to cell death. Expression of the mutant CGN in the inner ear results in severe hair cell death and hearing loss in mice, resembling the auditory phenotype in human patients. Interestingly, a human-specific residue (V1112) in the neopeptide generated by the frameshift mutation is critical for the aggregation and cytotoxicity of the mutant human CGN. Moreover, the expression of heat shock factor 1 (HSF1) decreases the accumulation of insoluble mutant CGN aggregates and rescues cell death. In summary, these findings identify mutant-specific toxic polypeptides as a disease-causing mechanism of the deafness mutation in CGN, which can be targeted by the expression of the cell chaperone response regulator HSF1.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

CGN

Basic Info

Related

Analysis