Erich E. Wanker
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View article: Chemical Targeting of the ATXN1 aa99–163 Interaction Site Suppresses polyQ-Expanded Protein Dimerization
Chemical Targeting of the ATXN1 aa99–163 Interaction Site Suppresses polyQ-Expanded Protein Dimerization Open
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a polyglutamine (polyQ) tract in the ATXN1 protein. This expansion is thought to be responsible for the gradual aggregation of the mutant protei…
View article: Chemical targeting of the ATXN1 aa99-163 interaction site suppresses polyQ-expanded protein dimerization
Chemical targeting of the ATXN1 aa99-163 interaction site suppresses polyQ-expanded protein dimerization Open
Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a polyglutamine (polyQ) tract in the ATXN1 protein. This expansion is thought to be responsible for the gradual aggregation of the mutant protei…
View article: Formation of amyloid-like HTTex1 aggregates in neurons, downregulation of synaptic proteins and early mortality of Huntington’s disease flies are causally linked
Formation of amyloid-like HTTex1 aggregates in neurons, downregulation of synaptic proteins and early mortality of Huntington’s disease flies are causally linked Open
Amyloidogenic mutant huntingtin exon-1 (mHTTex1) protein aggregates with pathogenic polyglutamine (polyQ) tracts are the potential root cause of Huntington’s disease (HD). Here, we assessed the gain-of-function toxicity of mHTTex1 aggregat…
View article: Cryo-electron tomography on synaptic vesicles isolated from mouse brain (part 1)
Cryo-electron tomography on synaptic vesicles isolated from mouse brain (part 1) Open
View article: Unraveling the interplay between tau seeding and autophagy processes
Unraveling the interplay between tau seeding and autophagy processes Open
Background The microtubule‐associated protein tau is the most commonly misfolded protein in neurodegenerative disorders including Alzheimer’s disease and other related tauopathies. These neurological illnesses are hypothesized to share a c…
View article: Molecular architecture of synaptic vesicles
Molecular architecture of synaptic vesicles Open
Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active zone for release by exocytosis. After release, SV proteins and excess membrane are recycled via endocytosis, and new SVs can be formed in a clathrin-de…
View article: AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain Inhibitors
AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain Inhibitors Open
Coronavirus disease 2019 (COVID-19) is caused by a new, highly pathogenic severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects human cells through its transmembrane spike (S) glycoprotein. The receptor-binding domain (…
View article: Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure
Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure Open
View article: Polyglutamine disease proteins: Commonalities and differences in interaction profiles and pathological effects
Polyglutamine disease proteins: Commonalities and differences in interaction profiles and pathological effects Open
Currently, nine polyglutamine (polyQ) expansion diseases are known. They include spinocerebellar ataxias (SCA1, 2, 3, 6, 7, 17), spinal and bulbar muscular atrophy (SBMA), dentatorubral‐pallidoluysian atrophy (DRPLA), and Huntington's dise…
View article: Molecular architecture of synaptic vesicles
Molecular architecture of synaptic vesicles Open
Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active zone for release by exocytosis. After release, SV proteins and excess membrane are recycled via endocytosis, and new SVs are formed in a clathrin-depen…
View article: AI-guided pipeline for protein–protein interaction drug discovery identifies a SARS-CoV-2 inhibitor
AI-guided pipeline for protein–protein interaction drug discovery identifies a SARS-CoV-2 inhibitor Open
View article: A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer’s disease
A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer’s disease Open
Background Alzheimer’s disease (AD) is characterized by the intra- and extracellular accumulation of amyloid-β (Aβ) peptides. How Aβ aggregates perturb the proteome in brains of patients and AD transgenic mouse models, remains largely uncl…
View article: Delineation of functional subdomains of Huntingtin protein and their interaction with HAP40
Delineation of functional subdomains of Huntingtin protein and their interaction with HAP40 Open
View article: AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor
AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor Open
Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that c…
View article: Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure
Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure Open
Expansion of the glutamine tract (poly-Q) in the protein Huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic in…
View article: Generation of an induced pluripotent stem cell line from a Huntington’s disease patient with a long HTT-PolyQ sequence
Generation of an induced pluripotent stem cell line from a Huntington’s disease patient with a long HTT-PolyQ sequence Open
View article: A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer’s disease
A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer’s disease Open
Background Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptides in intra- and extracellular deposits. How Aβ aggregates perturb the proteome in brains of patients and AD transgenic mouse models, however,…
View article: Additional file 3 of A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer’s disease
Additional file 3 of A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer’s disease Open
Additional file 3: Supplementary Excel File 1a. DEPs from 5xFAD versus wild-type tissue comparisons in hippocampus and cortex; DEPs were defined using the “pairwise model”; Supplementary Excel File 1b. Summary of the statistical calculatio…
View article: Delineation of Functional Subdomains of Huntingtin Protein and Their Interaction with Hap40
Delineation of Functional Subdomains of Huntingtin Protein and Their Interaction with Hap40 Open
View article: Early detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches
Early detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches Open
Huntingtin-lowering approaches that target huntingtin expression are a major focus for therapeutic intervention for Huntington’s disease. When the cytosine, adenine and guanine repeat is expanded, the huntingtin pre-mRNA is alternatively p…
View article: Expanding the Huntington’s disease research toolbox; validated subdomain protein constructs for biochemical and structural investigation of huntingtin
Expanding the Huntington’s disease research toolbox; validated subdomain protein constructs for biochemical and structural investigation of huntingtin Open
Huntington’s disease is characterised by CAG expansion in the huntingtin gene above a critical threshold of ~ 35 repeats, resulting in polyglutamine expansion of the huntingtin protein (HTT). The biological role of wildtype HTT and the ass…
View article: Generation of induced pluripotent stem cells from three individuals with Huntington‘s disease
Generation of induced pluripotent stem cells from three individuals with Huntington‘s disease Open
View article: Generation of four iPSC lines from four patients with Leigh syndrome carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6
Generation of four iPSC lines from four patients with Leigh syndrome carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6 Open
View article: Dynamics of huntingtin protein interactions in the striatum identifies candidate modifiers of Huntington disease
Dynamics of huntingtin protein interactions in the striatum identifies candidate modifiers of Huntington disease Open
View article: CellFIE: CRISPR- and Cell Fusion-based Two-hybrid Interaction Mapping of Endogenous Proteins
CellFIE: CRISPR- and Cell Fusion-based Two-hybrid Interaction Mapping of Endogenous Proteins Open
View article: Complete suppression of Htt fibrillization and disaggregation of Htt fibrils by a trimeric chaperone complex
Complete suppression of Htt fibrillization and disaggregation of Htt fibrils by a trimeric chaperone complex Open
View article: A quantitative mapping approach to identify direct interactions within complexomes
A quantitative mapping approach to identify direct interactions within complexomes Open
Complementary methods are required to fully characterize all protein complexes, or the complexome, of a cell. Affinity purification coupled to mass-spectrometry (AP-MS) can identify the composition of complexes at proteome-scale. However, …
View article: Small, Seeding-Competent Huntingtin Fibrils Are Prominent Aggregate Species in Brains of zQ175 Huntington’s Disease Knock-in Mice
Small, Seeding-Competent Huntingtin Fibrils Are Prominent Aggregate Species in Brains of zQ175 Huntington’s Disease Knock-in Mice Open
The deposition of mutant huntingtin (mHTT) protein aggregates in neurons of patients is a pathological hallmark of Huntington’s disease (HD). Previous investigations in cell-free and cell-based disease models showed mHTT exon-1 (mHTTex1) f…
View article: Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome
Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome Open
Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Using patient-…
View article: FEZ1 Forms Complexes with CRMP1 and DCC to Regulate Axon and Dendrite Development
FEZ1 Forms Complexes with CRMP1 and DCC to Regulate Axon and Dendrite Development Open
Elaboration of neuronal processes is an early step in neuronal development. Guidance cues must work closely with intracellular trafficking pathways to direct expanding axons and dendrites to their target neurons during the formation of neu…