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

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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 ...

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 ...

Realistic models of cellular environments have long captured the imagination of biologists and physical scientists. More than 20 years ago, Goodshellâ s inspiring rendering of cellular environments provided the foundation for the idea of capturing the ful ...

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 ...

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 ...

The proteolytic cleavage of the transmembrane (TM) domain of the amyloid precursor protein (APP) releases amyloid-beta (A beta) peptides, which accumulation in the brain tissue is an early indicator of Alzheimer's disease. We used multiscale molecular dyna ...

Passive immunization against toxic misfolded proteins could offer protection against neurodegenerative disease. LathuiliSre et al. report the development of a retrievable device to encapsulate cells secreting recombinant anti-amyloid-beta antibodies. When ...

Accumulation of amyloid-beta (A beta) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of A beta remains elusive although evidence suggests soluble oligomers may be prima ...

Amyloid-beta (A beta) peptide oligomerization plays a central role in the pathogenesis of Alzheimer's disease (AD), and A beta oligomers are collectively considered an appealing therapeutic target for the treatment of AD. However, the molecular mechanisms ...

The deposition of amyloid-beta (Aβ) aggregates in the brain is a major pathological hallmark of Alzheimer's disease (AD). Aβ is generated from the cleavage of C-terminal fragments of the amyloid precursor protein (APP-CTFs) by γ-secretase, an intramembrane ...

An important pathological hallmark of Alzheimer's disease (AD) is the deposition of amyloid-beta (A) peptides in the brain parenchyma, leading to neuronal death and impaired learning and memory. The protease -secretase is responsible for the intramembrane ...

Known gamma-secretase inhibitors or modulators display an undesirable pharmacokinetic profile and toxicity and have therefore not been successful in clinical trials for Alzheimer's disease (AD). So far, no compounds from natural products have been identifi ...

Background: Beside neurofibrillary tangles, amyloid plaques are the major histological hallmarks of Alzheimer's disease (AD) being composed of aggregated fibrils of beta-amyloid (A beta). During the underlying fibrillogenic pathway, starting from a surplus ...

Today, more than 40 million people worldwide are affected by neurodegenerative disorders. Onset of these diseases is associated with insoluble fibrillar protein aggregates, termed amyloids. The molecular origin and the link between amyloid formation and di ...

Alzheimer's disease (AD)-associated gamma-secretase is a ubiquitously expressed multi-subunit protease complex embedded in the lipid bilayer of cellular compartments including endosomes and the plasma membrane. Although gamma-secretase is of crucial intere ...

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

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

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

Studying membrane-protein interplay by modeling realistic conditions

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

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

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Amyloid-beta oligomerization is associated with the generation of a typical peptide fragment fingerprint

The adipocyte differentiation protein APMAP is an endogenous suppressor of Aβ production in the brain

Identification of new Presenilin-1 phosphosites: implication for gamma-secretase activity and A beta production

The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-beta peptides

Structural differences of amyloid-beta fibrils revealed by antibodies from phage display

New Insights Into Amyloid Formation and Structure by Innovative Atomic Force Microscopy Methods

Production of active glycosylation-deficient gamma-secretase complex for crystallization studies