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Do Lewy bodies contain alpha-synuclein fibrils? and Does it matter? A brief history and critical analysis of recent reports

Hilal Lashuel

Several lines of evidence from neuropathological studies, human genetics, in vitro aggregation studies and cellular and animal models support the hypothesis that aSyn plays a central role in the formation of Lewy pathologies. These are cytoplasmic proteina ...

2020

Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis

Andrea Cavalli, Alessio Mylonas, Martin Meyer

Systemic amyloidosis is a heterogeneous group of diseases associated with protein misfolding into insoluble beta-sheet rich structures that deposit extracellularly in different organs, eventually compromising their function. There are more than 30 differen ...

E M H SWISS MEDICAL PUBLISHERS LTD2020

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Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the ...

NATL ACAD SCIENCES2020

The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

Hilal Lashuel, Graham Knott, Marion Leleu, Fabien Kuttler, Anne-Laure Mahul Mellier, Johannes Burtscher, Niran Maharjan, Laura Emmeline H Weerens

Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, t ...

2020

One of the molecular hallmarks of amyloidoses is ordered protein aggregation involving the initial formation of soluble protein oligomers that eventually grow into insoluble fibrils. The identification and characterization of molecular species critical fo ...

2020

Endoplasmic Reticulum and Lysosomal Quality Control of Four Nonsense Mutants of Iduronate 2-Sulfatase Linked to Hunter's Syndrome

Maurizio Molinari, Andrea Cavalli

Hunter's syndrome (mucopolysaccharidosis type II) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. Motivated by the case of a child affected by this syndrome, we compared the intracellular fate of w ...

2020

A compelling link is emerging between the posttranslational modification O-GlcNAc and protein aggregation. A prime example is alpha-synuclein, which forms toxic aggregates that are associated with neurodegeneration in Parkinson's and related diseases. alph ...

NATL ACAD SCIENCES2019

Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is characterized by the deposition of two aggregated proteins: Amyloid beta (Aß) and hyperphosphorylated tau. Accumulations of these proteins are thought to be the signature ...

EPFL2019

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 ...

FRONTIERS MEDIA SA2019

Tauopathies are neurodegenerative diseases whose common pathological feature is the intraneuronal accumulation of tau aggregates. Tau protein has various roles in the neuron, among which stabilization of microtubules (MT), regulation of synaptic activity o ...

EPFL2019