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Chemical Structure| 128446-36-6 Chemical Structure| 128446-36-6
Chemical Structure| 128446-36-6

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Methyl-β-cyclodextrin is a cyclic heptasaccharide that delivers hydrophobic agents by solubilizing non-polar substances. It is also used extensively as a cholesterol-depleting reagent, significantly reducing clathrin-dependent endocytosis and blocking cell migrasome formation.

Synonyms: Methyl-beta-cyclodextrin; Randomly methylated β-cyclodextrin

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Product Citations

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Chen, Xi ; Wang, Ya-Juan ; Mu, Tingwei ;

Abstract: Gamma-aminobutyric acid type A receptors (GABAARs) are the major inhibitory neurotransmitter-gated channel in the mammalian central nervous system. GABAARs function as heteropentamers, typically composed of two α1, two β2, and one γ2 subunits. Protein homeostasis between GABAAR folding, trafficking, assembly, and degradation is critical to ensure normal physiological functions. Variants in genes encoded for GABAARs lead to numerous neurological disorders, such as genetic epilepsy with or without neurodevelopmental delay. While these variants are associated with severe clinical presentations of epilepsy, the molecular mechanisms driving the disease remain to be elucidated. In this study, we focused on four missense epilepsy-associated variants (EAVs) in the GABRB2 gene: Q209F210delinsH (c. 627_629del), R240T (c. 719G>C), I246T (c. 737T>C), and I299S (c. 896T>G). HEK293T cells exogenously expressing these β2 variants exhibited significantly reduced GABA-induced peak chloride current, indicating their loss of function. However, the four β2 EAVs differed in the degree of proteostasis deficiencies, including increased ER retention, compromised assembly, decreased protein stability, and reduced trafficking and surface expression, with Q209F210delinsH and R240T variants leading to the most severe degradation. Collectively, these results indicate that these epilepsy-linked variants have debilitating effects on the early biogenesis of the β2 subunit, causing misfolding, aggregation, and rapid degradation before it can be assembled with other subunits and transported to the plasma membrane. Overall, our work offers crucial mechanistic insight into how specific β2 missense variants impact the proteostasis maintenance of GABAARs, which could facilitate the development of effective therapeutics for genetic epilepsy by targeting trafficking-deficient GABAAR variants.

Keywords: GABAA receptor ; GABRB2 ; epilepsy ; missense variants ; proteostasis ; endoplasmic reticulum ; folding ; assembly ; trafficking ; degradation

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Product Details of Methyl-β-cyclodextrin

CAS No. :128446-36-6
Formula : N/A
M.W : 1303.30
SMILES Code : NONE
Synonyms :
Methyl-beta-cyclodextrin; Randomly methylated β-cyclodextrin
MDL No. :MFCD00074980

Safety of Methyl-β-cyclodextrin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H312-H319-H332
Precautionary Statements:P280-P305+P351+P338
 

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