Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds

• Published in: Nature (London) Vol. 575; no. 7781; pp. 203 - 209
• Main Authors: Li, Zhaoyang, Wang, Cen, Wang, Ziying, Zhu, Chenggang, Li, Jie, Sha, Tian, Ma, Lixiang, Gao, Chao, Yang, Yi, Sun, Yimin, Wang, Jian, Sun, Xiaoli, Lu, Chenqi, Difiglia, Marian, Mei, Yanai, Ding, Chen, Luo, Shouqing, Dang, Yongjun, Ding, Yu, Fei, Yiyan, Lu, Boxun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2019; Nature Publishing Group
• Subjects: 13/106; 13/89; 13/95; 132/122; 14/19; 631/154/1435/2163; 631/378/1689/1558; 631/61/32; 631/80/39; 631/92/507; 64/24; 64/60; 82/1; 82/58; 82/80; 96/109; 96/33; Alleles; Allelomorphism; Analysis; Animal models; Animals; Ataxin; Ataxin-3 - genetics; Autophagosomes - metabolism; Autophagy; Chemical compounds; Crosslinking; Disease Models, Animal; Drosophila melanogaster - genetics; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - chemistry; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drug Evaluation, Preclinical - methods; Female; Genetic aspects; Humanities and Social Sciences; Humans; Huntingtin; Huntingtin Protein - antagonists & inhibitors; Huntingtin Protein - chemistry; Huntingtin Protein - genetics; Huntingtin Protein - metabolism; Huntington's chorea; Huntington's disease; Huntingtons disease; Immunoassay; Influence; Kinases; Male; Mice; Microtubule-associated protein 1; Microtubule-Associated Proteins - genetics; multidisciplinary; Mutant Proteins - antagonists & inhibitors; Mutant Proteins - chemistry; Mutant Proteins - genetics; Mutant Proteins - metabolism; Mutants; Mutation - drug effects; Mutation - genetics; Neurodegeneration; Neurodegenerative diseases; Neurons - cytology; Peptides - genetics; Phagosomes; Phenotype; Phenotypes; Polyglutamine diseases; Proteins; Reproducibility of Results; Science; Science (multidisciplinary); Stem cells; Tethering; Trinucleotide repeat diseases; China

Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We hypothesized that compounds that interact with both the autophagosome protein microtubule-associated prote...