Won-Seok Lee

Keywords Animals, Ataxin-1, Cerebellum, Drosophila, Humans, Mice, Peptides, Spinocerebellar Ataxias, Transglutaminases, Genetics, Neuroscience, Genetic diseases, Molecular pathology, Neurodegeneration Abstract Many neurodegenerative disorders are caused by abnormal accumulation of misfolded proteins. In spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded (polyQ-expanded) ataxin-1 (ATXN1) causes neuronal toxicity.

Keywords Humans, PubMed, Databases, Factual Abstract In the effort to treat Mendelian disorders, correcting the underlying molecular imbalance may be more effective than symptomatic treatment. Identifying treatments that might accomplish this goal requires extensive and up-to-date knowledge of molecular pathways-including drug-gene and gene-gene relationships.

Results We first used conventional single-nucleus RNA sequencing (snRNA-seq)30,31 to analyze RNA expression in 581,273 nuclei sampled from the anterior part of the caudate nucleus—the largest component of the striatum and the region most affected in HD—from 50 persons with HD and 53 unaffected controls (mean 5,643 cell nuclei per donor) (Table S1). Each nucleus was assigned to one of seven major cell types, based on the RNAs it expressed (Figures 1A and S1).