Detection of alpha-rod protein repeats using a neural network and application to huntingtin by Palidwor, G, Shcherbinin, S, Huska, MR, Rasko, T, Stelzl, U, Arumughan, A, Foulle, R, Porras, P, Sanchez-Pulido, L, Wanker, E, Andrade-Navarro, M

“…This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. …”

A series of N-terminal epitope tagged <it>Hdh</it> knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis by Zheng Shuqiu, Ghitani Nima, Blackburn Jessica S, Liu Jeh-Ping, Zeitlin Scott O

Subjects: “…Huntingtin…”
Get full text

Full-length huntingtin is palmitoylated at multiple sites and post-translationally myristoylated following caspase-cleavage by Fanny L. Lemarié, Shaun S. Sanders, Yen Nguyen, Dale D. O. Martin, Michael R. Hayden

Subjects: “…huntingtin…”
Get full text

Control of the structural landscape and neuronal proteotoxicity of mutant Huntingtin by domains flanking the polyQ tract by Koning Shen, Barbara Calamini, Jonathan A Fauerbach, Boxue Ma, Sarah H Shahmoradian, Ivana L Serrano Lachapel, Wah Chiu, Donald C Lo, Judith Frydman

“…In Huntington’s disease (HD), neurotoxicity correlates with an increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. …”
Get full text

Mutant Huntingtin Derails Cysteine Metabolism in Huntington’s Disease at Both Transcriptional and Post-Translational Levels by Bindu D. Paul, Juan I. Sbodio, Solomon H. Snyder

“…We previously showed that the metabolism of cysteine is dysregulated in Huntington’s disease (HD), a neurodegenerative disorder triggered by the expansion of polyglutamine repeats in the protein huntingtin. In this study, we showed that cysteine metabolism is compromised at multiple levels in HD, both transcriptional and post-translational. …”
Get full text

Polyglutamine- and temperature-dependent conformational rigidity in mutant huntingtin revealed by immunoassays and circular dichroism spectroscopy. by Valentina Fodale, Natalie C Kegulian, Margherita Verani, Cristina Cariulo, Lucia Azzollini, Lara Petricca, Manuel Daldin, Roberto Boggio, Alessandro Padova, Rainer Kuhn, Robert Pacifici, Douglas Macdonald, Ryan C Schoenfeld, Hyunsun Park, J Mario Isas, Ralf Langen, Andreas Weiss, Andrea Caricasole

“…BACKGROUND:In Huntington's disease, expansion of a CAG triplet repeat occurs in exon 1 of the huntingtin gene (HTT), resulting in a protein bearing>35 polyglutamine residues whose N-terminal fragments display a high propensity to misfold and aggregate. …”
Get full text

Mutant huntingtin confers cell-autonomous phenotypes on Huntington’s disease iPSC-derived microglia by Nina Stöberl, Jasmine Donaldson, Caroline S. Binda, Branduff McAllister, Hazel Hall-Roberts, Lesley Jones, Thomas H. Massey, Nicholas D. Allen

“…Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by a dominantly inherited CAG repeat expansion in the huntingtin gene (HTT). Neuroinflammation and microglia have been implicated in HD pathology, however it has been unclear if mutant HTT (mHTT) expression has an adverse cell-autonomous effect on microglial function, or if they are only activated in response to the neurodegenerative brain environment in HD. …”
Get full text

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! by Claudia Riccardi, Federica D’Aria, Dominga Fasano, Filomena Anna Digilio, Maria Rosaria Carillo, Jussara Amato, Laura De Rosa, Simona Paladino, Mariarosa Anna Beatrice Melone, Daniela Montesarchio, Concetta Giancola

“…Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. …”
Get full text

Elucidating the Influence of Lipid Composition on Bilayer Perturbations Induced by the N-Terminal Region of the Huntingtin Protein by Yasith Indigahawela Gamage, Jianjun Pan

“…Understanding the membrane interactions of the N-terminal 17 residues of the huntingtin protein (HttN) is essential for unraveling its role in cellular processes and its impact on huntingtin misfolding. …”
Get full text

Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE by Meili Liu, Zhe Huai, Hongwei Tan, Guangju Chen

“…AMPylation is a prevalent posttranslational modification that involves the addition of adenosine monophosphate (AMP) to proteins. Exactly how Huntingtin-associated yeast-interacting protein E (HYPE), as the first human protein, is involved in the transformation of the AMP moiety to its substrate target protein (the endoplasmic reticulum chaperone binding to immunoglobulin protein (BiP)) is still an open question. …”
Get full text

The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin by Azzam Aladdin, Yanhua Yao, Ciyu Yang, Günther Kahlert, Marvi Ghani, Nikolett Király, Anita Boratkó, Karen Uray, Gunnar Dittmar, Krisztina Tar

Subjects: Get full text

A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles. by Amy L Lee, Hailey M Ung, L Paul Sands, Elise A Kikis

“…One such disorder is Huntington's Disease (HD) that is caused by a polyglutamine expansion in the human huntingtin protein (htt). The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. …”
Get full text

Benefits of global mutant huntingtin lowering diminish over time in a Huntington’s disease mouse model by Deanna M. Marchionini, Jeh-Ping Liu, Alberto Ambesi-Impiombato, Kimberly Kerker, Kim Cirillo, Mukesh Bansal, Rich Mushlin, Daniela Brunner, Sylvie Ramboz, Mei Kwan, Kirsten Kuhlbrodt, Karsten Tillack, Finn Peters, Leena Rauhala, John Obenauer, Jonathan R. Greene, Christopher Hartl, Vinod Khetarpal, Brenda Lager, Jim Rosinski, Jeff Aaronson, Morshed Alam, Ethan Signer, Ignacio Muñoz-Sanjuán, David Howland, Scott O. Zeitlin

“…We have developed an inducible Huntington’s disease (HD) mouse model that allows temporal control of whole-body allele-specific mutant huntingtin (mHtt) expression. We asked whether moderate global lowering of mHtt (~50%) was sufficient for long-term amelioration of HD-related deficits and, if so, whether early mHtt lowering (before measurable deficits) was required. …”
Get full text

Huntingtin and Other Neurodegeneration-Associated Proteins in the Development of Intracellular Pathologies: Potential Target Search for Therapeutic Intervention by Aleksandra S. Churkina (Taran), Anton S. Shakhov, Anatoly A. Kotlobay, Irina B. Alieva

Subjects: Get full text

Haplotyping SNPs for allele-specific gene editing of the expanded huntingtin allele using long-read sequencing by Li Fang, Alex Mas Monteys, Alexandra Dürr, Megan Keiser, Congsheng Cheng, Akhil Harapanahalli, Pedro Gonzalez-Alegre, Beverly L. Davidson, Kai Wang

“…Summary: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG trinucleotide repeat expansions in exon-1 of huntingtin (HTT). Currently, there is no cure for HD, and the clinical care of individuals with HD is focused on symptom management. …”
Get full text

Large-scale RNA interference screening in mammalian cells identifies novel regulators of mutant huntingtin aggregation. by Tomoyuki Yamanaka, Hon Kit Wong, Asako Tosaki, Peter O Bauer, Koji Wada, Masaru Kurosawa, Tomomi Shimogori, Nobutaka Hattori, Nobuyuki Nukina

“…We here perform RNAi screening in mouse neuro2a cells to identify mammalian modifiers for aggregation of mutant huntingtin, a causative protein of HD. By systematic cell transfection and automated cell image analysis, we screen ∼ 12000 shRNA clones and identify 111 shRNAs that either suppress or enhance mutant huntingtin aggregation, without altering its gene expression. …”
Get full text

Rhes depletion promotes striatal accumulation and aggregation of mutant huntingtin in a presymptomatic HD mouse model by Yongcheng Pan, Yongcheng Pan, Beisha Tang, Beisha Tang, Beisha Tang, Xiao-Jiang Li, Shihua Li, Shihua Li, Qiong Liu, Qiong Liu

“…Additionally, Rhes deletion in 22-week-old HD KI mice resulted in increased P62 levels, reduced LC3-II levels, and unchanged phosphorylation of mTOR and beclin-1, unchanged mTOR protein level, except for a decrease in beclin-1.DiscussionOur findings suggest that knockdown Rhes promotes striatal aggregation of mutant huntingtin by reducing autophagy activity in a mTOR-independent manner. …”
Get full text

Circadian Clocks Function in Concert with Heat Shock Organizing Protein to Modulate Mutant Huntingtin Aggregation and Toxicity by Fangke Xu, Elzbieta Kula-Eversole, Marta Iwanaszko, Alan L. Hutchison, Aaron Dinner, Ravi Allada

“…Studies indicate that mutant Huntingtin (mHtt), the cause of Huntington’s disease (HD), disrupts circadian rhythms often before motor symptoms are evident. …”
Get full text

GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling by Ching-Chi Chang, Tzu-Chin Lin, Hsiao-Li Ho, Chien-Yin Kuo, Hsin-Hua Li, Tatiana A. Korolenko, Wei-Jen Chen, Te-Jen Lai, Ying-Jui Ho, Chih-Li Lin

Subjects: Get full text

Selective observation of semi-rigid non-core residues in dynamically complex mutant huntingtin protein fibrils by Irina Matlahov, Jennifer C. Boatz, Patrick C.A. van der Wel

“…This challenge is exemplified by mutant huntingtin exon 1 (HttEx1), which self-assembles into pathogenic neuronal inclusions in Huntington disease (HD). …”
Get full text