Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

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Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to represent extreme ends of a disease spectrum, which encompasses ALS with cognitive/behavioral ...

Neurodegenerative diseases (NDDs), such as Parkinson's disease and Alzheimer's disease present a significant global health concern. The misfolding of proteins from native disordered monomeric forms into beta-sheet enriched aggregates of oligomers and fibri ...

Chromatin-modifying enzymes target distinct residues within histones to finetune gene expression profiles. SIRT7 is an NAD+-dependent deacylase often deregulated in cancer, which deacetylates either H3 lysine 36 (H3K36) or H3K18 with high specificity withi ...

Chaperones ensure protein homeostasis and are conserved across species. The ATP-dependent chaperone Hsp90 is present from bacteria to eukaryotes, where it stabilizes and activates a wide range of substrate proteins called clients. However, what determines ...

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance amo ...

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

This spreading of prion proteins is at the basis of brain neurodegeneration. This paper deals with the numerical modelling of the misfolding process of a-synuclein in Parkinson's disease. We introduce and analyse a discontinuous Galerkin method for the sem ...

Amyloid-forming proteins such alpha-synuclein and tau, which are implicated in Alzheimer's and Parkinson's disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determin ...

The myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission of electrical impulses and are often differentially affected in human neurodegenerative diseases across CNS region, age and sex. We hypothesize that ...

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and elec ...

Phantom boarder (PB) is the sensation that someone uninvited is in the patient's home despite evidence to the contrary. It is mostly reported by patients with neurodegenerative disorders such as Alzheimer's disease, dementia with Lewy bodies or Parkinson's ...

Neuropathological tau tangles in Alzerheimer’s disease (AD) have been roughly characterized into pre‐tangles, mature tangles and ghost tangles. However, to date, their maturation in the human brain is poorly understood. Here, we aimed to define the structu ...

The spinal cord is an elongated nervous structure that together with the brain forms the central nervous system. It relays sensory and motor information between the brain and the body, thus controlling most somatic and autonomic body functions. In recent y ...

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

JC polyomavirus (JCPyV) is an opportunistic virus that remains in a latent state in the kidneys and lymphoid organs of more than half of the human adult population. In rare cases of severe immune suppression, the virus is able to establish a lytic infectio ...

Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is the aromatic side chain of Tyr, which undergoes modifications such as phosphorylation and ...

The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

Huntington's disease (HD) is a devastating neurodegenerative disorder marked by the accumulation of Huntingtin protein (HTT) fragments in HD neuronal cells. These aggregates are predominantly composed of polyglutamine (polyQ)-containing HTT N-terminal frag ...

TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

Amyloidosis refers to a range of medical conditions in which misshapen proteins accumulate in various organs and tissues, forming insoluble fibrils. Cardiac amyloidosis is frequently linked to the buildup of misfolded transthyretin (TTR) or immunoglobulin ...

Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Chattez avec Graph Search

Longitudinal changes in MEG-based brain network topology of ALS patients with cognitive/behavioral impairment—An exploratory study

Nanoplasmonic infrared biosensors enabling detection of misfolded protein biomarkers and drug screening for neurodegenerative diseases

Structural basis of SIRT7 nucleosome engagement and substrate specificity

Subtle variations in a client protein determine bacterial Hsp90 dependence

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases

Deconstructing and Reconstructing the Complexity of Tau pathology

Discontinuous Galerkin methods for Fisher-Kolmogorov equation with application to a-synuclein spreading in Parkinson's disease

O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology

Brain matters: unveiling the distinct contributions of region, age, and sex to glia diversity and CNS function

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy

Phantom Boarder Relates to Experimentally‐Induced Presence Hallucinations in Parkinson's Disease

Ultrastructural characterization of tau pathology in the human post‐mortem Alzheimer’s disease brain

Digital reconstruction of the mammalian spinal cord: from anatomical reference volume to cell type atlas of the mouse spinal cord

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles

A Versatile Method for Site-Specific Chemical Installation of Aromatic Posttranslational Modification Analogs into Proteins

Coordination of protein synthesis and degradation in mammalian cells

Exploring the therapeutic potential of Huntingtin native state stabilization through targeting its interacting partners

Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro

Classification of patients with cardiac amyloidosis using machine learning models on Italian electronic clinical health records