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gamma-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site

Publications associées (43)

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The Gamma-Secretase-Mediated Proteolytic Processing of APP C-Terminal Fragments as a Therapeutic Target for Alzheimer's Disease

Jemila Houacine

Alzheimer's disease (AD) is a devastating neurodegenerative disorder which severely impairs cognitive functions by triggering neuronal cell death and synaptic loss, and finally leads the patients to death. Two main histopathological hallmarks can be found ...

EPFL2011

The causes of sporadic Alzheimer's Disease (AD), the most common form of dementia at old age, are still unknown. Familial early onset AD (FAD) is mainly caused by mutations of Presenilins (PS), the active subunits of γ-secretase. Processing of its substrat ...

EPFL2011

There is emerging evidence implicating a role for the autophagy-ysosome pathway in the pathogenesis of Lewy body disease. We investigated potential neuropathologic and biochemical alterations of autophagy-lysosome pathway-related proteins in the brains of ...

Lippincott, Williams & Wilkins2011

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Phosphorylation of alpha-synuclein (alpha-syn) at Ser-129 is a hallmark of Parkinson disease and related synucleinopathies. However, the identity of the natural kinases and phosphatases responsible for regulating alpha-syn phosphorylation remain unknown. H ...

American Society for Biochemistry and Molecular Biology2010

Novel gamma-secretase inhibitors uncover a common nucleotide-binding site in JAK3, SIRT2, and PS1

Patrick Fraering, Nikita Rudinskiy, Claude André Schweizer

Gamma-secretase is an intramembrane-cleaving protease responsible for the final proteolytic event in the production of the amyloid-beta peptides (Abeta) implicated in Alzheimer's disease (AD). Inhibition of gamma-secretase activity is thus an attractive th ...

2010

Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution

Lorène Aeschbach, Patrick Fraering, Hua Li

Gamma-secretase, an integral membrane protein complex, catalyzes the intramembrane cleavage of the beta-amyloid precursor protein (APP) during the neuronal production of the amyloid beta-peptide. As such, the protease has emerged as a key target for develo ...

Elsevier2009

Palmitoylation cycles and regulation of protein function (Review)

Steinunn Baekkeskov Hanahan

The efficacy and success of many cellular processes is dependent on a tight orchestration of proteins trafficking to and from their site(s) of action in a time-controlled fashion. Recently, a dynamic cycle of palmitoylation/de-palmitoylation has been shown ...

Taylor & Francis2009

mTOR complex 2 in adipose tissue negatively controls whole- body growth

Johan Auwerx

Mammalian target of rapamycin (mTOR), a highly conserved protein kinase that controls cell growth and metabolism in response to nutrients and growth factors, is found in 2 structurally and functionally distinct multiprotein complexes termed mTOR complex 1 ...

2009

Rapid purification of active gamma-secretase, an intramembrane protease implicated in Alzheimer's disease

Lorène Aeschbach, Patrick Fraering, Hua Li

Gamma-secretase is an unconventional aspartyl protease that processes many type 1 membrane proteins within the lipid bilayer. Because its cleavage of amyloid-beta precursor protein generates the amyloid-beta protein (Abeta) of Alzheimer's disease, partiall ...

Wiley-Blackwell2008

An overview of the fission yeast septation initiation network (SIN)

Viesturs Simanis, Andrea Krapp

The fission yeast septation initiation network, or SIN, is a signal transduction network that is required for septum formation in Schizosaccharomyces pombe. Its activity is tightly regulated through the cell cycle, to ensure proper co-ordination of mitosis ...

2008