Concept

Gamma secretase

Related publications (66)

Resistance mechanism to Notch inhibition and combination therapy in human T cell acute lymphoblastic leukemia

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy caused by acquisition of genetic alterations during T-cell development. The 5-year overall survival of pediatric T-ALL patients has improved considerably over the past 30 ...

EPFL2023

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

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

Molecular dissection of amyloid disaggregation by human HSP70

Paolo De Los Rios, Alessandro Barducci

The molecular steps that lead to the disaggregation of amyloid fibrils are shown to involve the synergistic action of HSP70 and its co-chaperones DNAJB1 and HSP110. The deposition of highly ordered fibrillar-type aggregates into inclusion bodies is a hallm ...

NATURE RESEARCH2020

Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Henning Paul-Julius Stahlberg, Ricardo Cesar Guerrero Ferreira, Pratibha Kumari

Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson’s disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1–121), composed of two protofibrils that a ...

2019

Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by -Secretase and Amyloid- Peptide Production

Patrick Fraering, Mitko Dimitrov, Hermeto Gerber, Guillermo Miguel Garcia Osuna

Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid- peptid ...

Amer Soc Biochemistry Molecular Biology Inc2017

Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials

Peter Frey, Jeffrey Alan Hubbell, Hans Mattias Larsson, Priscilla Suhasna Maithili Briquez, Kristen Lorentz

Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine or ...

2017

Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells

Patrick Fraering

Deregulation of the TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases (RTKs) has recently been demonstrated to predominately promote survival and chemoresistance of cancer cells. Intramembrane proteolysis mediated by presenilin/gamma-secretas ...

Federation Amer Soc Exp Biol2017

The lipidome associated with the gamma-secretase complex is required for its integrity and activity

Henning Paul-Julius Stahlberg, Patrick Fraering, Hermeto Gerber, Guillermo Miguel Garcia Osuna

gamma-Secretase is a multi-subunit membrane protease complex that catalyses the final intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of amyloid-beta peptides (A beta), which are implicated as the causative ...

Portland Press Ltd2016

Endogenous Regulators of Gamma-Secretase and Amyloid-Beta Production, and Engineering of Alzheimer's Disease Therapeutic Tools

Sébastien Mosser

Alzheimer s disease (AD) is a devastating neurodegenerative disease characterized by strong cognitive impairment and memory loss. These symptoms are caused by neuronal death, induced by two pathological hallmarks: extracellular senile plaques composed of a ...

EPFL2016

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