Relation of Antigliadin Antibodies to Gluten-Sensitive Enteropathy
Tadeusz P. Chorzelski, Ernst H. Beutner, Vijay Kumar, Tadeusz K. Zalewski in Serologic Diagnosis of Celiac Disease, 2020
These structures, be they primary, secondary, tertiary, or even quaternary, are unique for the different gliadin proteins. This means that the gliadin proteins are heterogeneous for parts of the molecule and, consequently, differ in physical and chemical properties. One of these properties is the polarity of the different parts of the molecule. In general, gliadin contains many neutral amino acids and, thus, has large hydrophobic regions in the molecule. The regions of polyglutamine that can be found in the molecule and the proline-containing regions are especially hydrophobic. Interaction with other hydrophobic molecules can be explained in this way. Aggregation also depends on the low charge of the gliadin molecules. The tertiary and quaternary shape of the molecule is based on the same principles, apart from the high proline content that prevents the formation of α-helix structures over larger parts of the molecule. About 13% of the gliadin molecule is in the α-helix form, whereas 58% of the molecule consists of β-turns. The remaining part has a random structure. These forms have consequences for the immunogenicity of the different molecules. β-Turns are especially immunogenetic and are found in the more nonpolar parts of the gliadin molecules.
Vitamin C in Neurological Function and Neurodegenerative Disease
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
HD is caused by an expanded (≥40) cytosine-adenine-guanine (CAG) trinucleotide repeat in exon 1 of the Huntingtin (HTT) gene [123,124]. This genetic mutation encodes for an expanded polyglutamine (polyQ) region near the N-terminus of the HTT protein. The precise function of wild-type (WT) HTT protein is uncertain. It is essential for development, demonstrated by embryonic lethality observed in mice homozygous null for Htt [125], and broadly necessary for neural maintenance [126,127]. HTT is a large protein (348 kDa), and through interactions with nearly 200 proteins [128–130], it plays a role in vesicle trafficking and axonal transport [131–133], transcriptional regulation [134–137], autophagy [138–140], and cell survival [125,136,141]. Many of these functions and protein-protein interactions, particularly those related to transcription regulation and cell signaling, depend on the nonexpanded polyQ tract (<35 repeats) present in wild-type HTT [119,142,143]. When mutated, the elongated polyQ tract not only interferes with normal HTT function but also leads to the formation of toxic cytosolic and nuclear protein aggregates [133,144–147].
Caenorhabditis elegans Aging is Associated with a Decline in Proteostasis
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Polyglutamine (polyQ) disorders are a family of nine different neurodegenerative disorders all of which are caused by an expansion of a polyQ tract, albeit in different proteins, each encoded by a cytosine-adenine-guanine (CAG) trinucleotide repeat in the corresponding gene. As such, these are heritable genetic disorders and include HD, Machado–Joseph disease (MJD), spinobulbar muscular atrophy (SBMA), dentatorubral–pallidoluysian atrophy (DRPLA), and five SCAs. For all of these diseases, the polyQ expansion destabilizes the affected protein thereby disrupting the thermodynamics of folding and causing protein misfolding and aggregation. Outside of the polyQ tract itself, each of the affected proteins in each of these diseases share no common sequences or functions. The key to disease is thus the polyQ tract, such that the age of disease onset and symptom severity is inversely proportional to the length of the polyQ tract [21–23].
Discovery of drugs that directly target the intrinsically disordered region of the androgen receptor
Published in Expert Opinion on Drug Discovery, 2020
AR-NTD is largely unstructured and described as having limited stable secondary structure which can be induced by interactions with binding partners to increase α-helical content and thereby conforms to a molten-globule-like conformation referred to as ‘collapsed disordered’ [13–15] (Figure 2(a)). This domain is the most abundantly post-translationally modified of the AR and acts as a hub for interactions with many other proteins (Figure 2(b)). Most importantly is interaction of this domain with the basal transcriptional machinery that is necessary for its transcriptional activity. Within AR-NTD is AF-1 which is estimated to have 13% helical secondary structure but this can increase upon interaction with a binding partner [13,14]. AF-1 is comprised of two transactivation units 1 and 5 (Tau-1 and Tau-5). Tau-1 is comprised of amino acid residues 101–370 of which a large number are acidic amino acids. Tau-5 is comprised of amino acid residues 360–485 and is not acidic. Interestingly AR-NTD harbors several repeat regions for glutamine (polyglutamine tract or polyQ), proline, alanine, and glycine.
RNA-seq analysis of testes from flurochloridone-treated rats
Published in Toxicology Mechanisms and Methods, 2020
Su Zhou, Rui Li, Wanwan Hou, Yue Wang, Suhui Zhang, Ying Yu, Lei Zhang, Hongyan Zhu, Zhichao Zhang, Jing Fang, Xiuli Chang, Yubin Zhang, Luqing Liu, Liming Tang, Zhijun Zhou
Huntington’s disease is a kind of neurodegenerative disorder of the central nervous system, caused by an expanded CAG triplet repeat in the Huntington gene, which leads to an expanded polyglutamine stretch in the Huntington protein (Mccolgan and Tabrizi 2010; Ha and Fung 2012). DEGs gathered in Huntington’s disease pathways indicated that FLC may affect neural system development in rats. Huntington’s disease is an autosomal dominant inheritance disease, implying that FLC may have a potential impact on fetal brain development. However, our results of FLC treatment in early embryonic development (Li et al. 2019) and embryo-fetal development assessments found no adverse effect on fetal brain development. Therefore, we will focus on the level of neurokines in fetal brain development in further research.
Advances in the understanding of hereditary ataxia – implications for future patients
Published in Expert Opinion on Orphan Drugs, 2018
Anna Zeitlberger, Heather Ging, Suran Nethisinghe, Paola Giunti
A plethora of causative mutations have been described in dominant inherited ataxias, including: conventional mutations (SCA5, SCA11, SCA13, SCA14, SCA19/22, SCA23, SCA26, SCA27, SCA28, SCA19, SCA35); rearrangements (SCA15, SCA16, SCA20); as well as expansions of variable length in intronic (SCA8, SCA10, SCA12, SCA31, SCA36) and exonic regions (SCA1, SCA2, SCA3, SAC6, SCA7, SCA17, DRPLA) [23]. The latter encompass the most common and best-studied dominantly inherited ataxias. Together with other late-onset neurodegenerative diseases, namely HD and spinal-bulbar muscular atrophy, they form the group of nine known polyglutamine (polyQ) diseases. These disorders share an exonic (CAG)n TR expansion in their respective disease genes [24–26]. Simple repetitive elements are considered pathological if the number of triplets is greater than the number found in wild-type alleles [27]. Once above a critical threshold, the excessive polyQ stretches in the translated proteins promote cell-specific degeneration associated with a toxic gain-of-function at the protein and mRNA level, which leads to the pathological hallmark of these disorders, cellular aggregation [28].