Development of novel methods and tools to decipher the huntingtin post-translation modifications code

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Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

Autophagy is a highly conserved process by which long-lived macromolecules, protein aggregates and dysfunctional/damaged organelles are delivered to lysosomes for degradation. Autophagy plays a crucial role in regulating protein quality control and cell ho ...

Huntington’s Disease (HD) is an inherited fatal neurodegenerative disease caused by a CAG expansion (36) in the first exon of the HD gene, resulting in the expression of the Huntingtin protein (Htt) or N-terminal fragments thereof with an expanded polygl ...

As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of mo ...

The misfolding and self-assembly of proteins into fibrils is a hallmark of several neurodegenerative and systemic diseases. These disease-associated proteins have the propensity to form fibrils with a cross-Î² sheet structure, called amyloids. Amyloids can ...

Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable he ...

The microtubule-associated protein Tau plays a central role in neurodegeneration and is a leading therapeutic target for the treatment of Alzheimer’s disease (AD). Several lines of evidence suggest that post-translational modifications (PTMs) regulate the ...

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of exon 1 of the Huntingtin protein (Httex1) play important roles in modulating its cellular properties and functions in health and disease. In particular, phosphorylation of th ...

Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson’s disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major ...

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving loss of motor neurons and having no known cure and uncertain etiology. Several studies have drawn connections between altered retrotransposon expression and ALS. C ...

Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that ...

Huntington Disease (HD) is caused by a CAG repeat expansion in the huntingtin gene leading to the formation of mutant Huntingtin protein (Htt) with an expanded polyglutamine (polyQ) domain (>36Q). Generation of short N-terminal Htt fragments by proteolysis ...

Posttranslational modifications can have profound effects on the biological and biophysical properties of proteins associated with misfolding and aggregation. However, their detection and quantification in clinical samples and an understanding of the mecha ...

The recognition of pathogen-derived nucleic acids is a critical mechanism by which the innate immune system detects viral infection. Upon activation, nucleic acid sensors initiate the expression of type I interferons and other inflammatory mediators, subse ...

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free ...

Huntington’s disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). A popular hypothesis is that the Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 3 ...

Chromatin is the template on which DNA-associated transactions take place in eukaryotic organisms. Nucleosomes consisting of the four histones H2A, H2B, H3 and H4 each organize ~150bp of DNA and constitute a first layer of chromatin. The three-dimensional ...

Accumulation and aggregation of misfolded alpha-synuclein is believed to be a cause of Parkinson's disease (PD). Phosphorylation of alpha-synuclein at S129 is known to be associated with the pathological misfolding process, but efforts to investigate the r ...

Development of novel methods and tools to decipher the huntingtin post-translation modifications code

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TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Autophagy and LRRK2 in the Aging Brain

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

Gold nanoparticles as a new tool in amyloid studies

Dynamic protein-chromatin interactions in heterochromatin and during the DNA damage response on the single molecule level

Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States

Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases

Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Properties of LINE-1 proteins and repeat element expression in the context of amyotrophic lateral sclerosis

Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models

The role of the polyglutamine and N-terminal domains in regulating the aggregation and structural properties of Huntingtin Exon 1

Phosphorylation of huntingtin at residue T3 is decreased in Huntington’s disease and modulates mutant huntingtin protein conformation

Identification and characterisation of small-molecule inhibitors targeting STING

The gut microbiota influences skeletal muscle mass and function in mice

Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths

Heterochromatin protein 1 recruitment and chromatin conformational dynamics at the single-molecule level

Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay