A subcutaneous cellular implant for passive immunization against amyloid-beta reduces brain amyloid and tau pathologies

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Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Melek Firat Altay

Synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy (MSA) are detrimental neurodegenerative diseases. Alpha-synuclein (aSyn), the main aggregating protein found in the pathological inclusions of these ailmen ...

EPFL2022

Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates

Grégoire Courtine, Tomislav Milekovic, Flavio Raschella

Progressive supranuclear palsy is a primary tauopathy affecting both neurons and glia and is responsible for both motor and cognitive symptoms. Recently, it has been suggested that progressive supranuclear palsy tauopathy may spread in the brain from cell ...

OXFORD UNIV PRESS2022

Towards elucidating the structural and cellular determinants of a-synuclein seeding and toxicity

Somanath Jagannath

Although it has been nearly two and half decades since the discovery of alpha-synuclein (aSyn) as the major component of Lewy bodies (LBs), our understanding of the involvement of different aSyn species, their seeding, spreading and toxicity in Parkinson's ...

EPFL2022

Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders

Hilal Lashuel, Melek Firat Altay

Alpha-synuclein (aSyn) is a pre-synaptic monomeric protein that can form aggregates in neurons in Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), and in oligodendrocytes in multiple system atrophy (MSA ...

BMC2022

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70

Paolo De Los Rios, Satyam Tiwari, Pierre Goloubinoff, Bruno Claude Daniel Fauvet, Salvatore Assenza

Detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the lack of a comprehensive characterization of the aggregates, which are typically heterogeneous. Here we designed a reporter chaper ...

NATURE PORTFOLIO2022

Novel trehalose-based excipients for stabilizing nebulized anti-SARS-CoV-2 antibody

Sandrine Gerber, François Rémi Pierre Noverraz, Solène Marcelle Françoise Marie Passemard

COVID-19 is caused by the infection of the lungs by SARS-CoV-2. Monoclonal antibodies, such as sotrovimab, showed great efficiency in neutralizing the virus before its internalization by lung epithelial cells. However, parenteral routes are still the prefe ...

2023

Enhancing mitochondrial quality control to fight neuromuscular degeneration in aging and disease

Mario Romani

Loss of mitochondrial function and proteostasis typify aging and age-associated degenerative disorders such as Alzheimer's disease and muscle aging. To date, no cure or preventive measure is available to manage these conditions. Alterations of cellular pro ...

EPFL2021

To target Tau pathologies, we must embrace and reconstruct their complexities

Hilal Lashuel, Galina Limorenko

The accumulation of hyperphosphorylated fibrillar Tau aggregates in the brain is one of the defining hallmarks of Tauopathy diseases, including Alzheimer's disease. However, the primary events or molecules responsible for initiation of the pathological Tau ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2021

Structural strains of misfolded tau protein define different diseases

Henning Paul-Julius Stahlberg

In diseases called tauopathies, misfolded tau proteins form aggregates called fibrils. Fibrils from nine different tauopathies show that tau misfolds in many ways, enabling the diseases to be classified according to fibril structure. ...

2021

An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer's disease

Mojgan Masoodi, Christopher Clark

Background Multiple pathophysiological processes have been described in Alzheimer's disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypot ...

2021

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Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders

Hilal Lashuel, Melek Firat Altay

BMC2022