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Article
Open AccessA novel human tau knock-in mouse model reveals interaction of Abeta and human tau under progressing cerebral amyloidosis in 5xFAD mice
Hyperphosphorylation and intraneuronal aggregation of the microtubule-associated protein tau is a major pathological hallmark of Alzheimer’s disease (AD) brain. Of special interest is the effect of cerebral am...
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Article
Open AccessHelical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor
The zinc-dependent metalloprotease meprin α is predominantly expressed in the brush border membrane of proximal tubules in the kidney and enterocytes in the small intestine and colon. In normal tissue homeosta...
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Article
Open AccessA glutaminyl cyclase-catalyzed α-synuclein modification identified in human synucleinopathies
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies ...
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Article
Open AccessTargeting isoaspartate-modified Aβ rescues behavioral deficits in transgenic mice with Alzheimer’s disease-like pathology
Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer’s disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evi...
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Article
Open AccessDevelopment of the clinical candidate PBD-C06, a humanized pGlu3-Aβ-specific antibody against Alzheimer’s disease with reduced complement activation
In clinical trials with early Alzheimer’s patients, administration of anti-amyloid antibodies reduced amyloid deposits, suggesting that immunotherapies may be promising disease-modifying interventions against ...
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Article
Open AccessEffector function of anti-pyroglutamate-3 Aβ antibodies affects cognitive benefit, glial activation and amyloid clearance in Alzheimer’s-like mice
Pyroglutamate-3 Aβ (pGlu-3 Aβ) is an N-terminally truncated and post-translationally modified Aβ species found in Alzheimer’s disease (AD) brain. Its increased peptide aggregation propensity and toxicity make ...
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Heterologous Expression of the Astacin Protease Meprin β in Pichia pastoris
Meprins are zinc-dependent proteases of the metzincin superfamily of metalloproteases. The enzymes are extracellular multi-domain proteins which are stabilized by disulfide bridges, dimerization, and glycosyla...
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Article
Open AccessIsoglutaminyl cyclase contributes to CCL2-driven neuroinflammation in Alzheimer’s disease
The brains of Alzheimer’s disease (AD) patients are characterized by deposits of Abeta peptides and by accompanying chronic inflammation. Here, we provide evidence that the enzyme isoglutaminyl cyclase (isoQC)...
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Article
Open AccessGlutaminyl cyclase-mediated toxicity of pyroglutamate-beta amyloid induces striatal neurodegeneration
Posttranslational modifications of beta amyloid (Aβ) have been shown to affect its biophysical and neurophysiological properties. One of these modifications is N-terminal pyroglutamate (pE) formation. Enzymati...
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Article
A quantitative analysis of spontaneous isoaspartate formation from N-terminal asparaginyl and aspartyl residues
The formation of isoaspartate (isoAsp) from asparaginyl or aspartyl residues is a spontaneous post-translational modification of peptides and proteins. Due to isopeptide bond formation, the structure and possi...
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Article
Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β
It is shown that the formation of amyloid-β oligomers, one of the histopathological signatures of Alzheimer’s disease, can be triggered by small quantities of a specifically truncated and post-translationally ...
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Article
Open AccessGlutaminyl cyclase contributes to the formation of focal and diffuse pyroglutamate (pGlu)-Aβ deposits in hippocampus via distinct cellular mechanisms
In the hippocampal formation of Alzheimer’s disease (AD) patients, both focal and diffuse deposits of Aβ peptides appear in a subregion- and layer-specific manner. Recently, pyroglutamate (pGlu or pE)-modified...
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Article
Open AccessDistinct glutaminyl cyclase expression in Edinger–Westphal nucleus, locus coeruleus and nucleus basalis Meynert contributes to pGlu-Aβ pathology in Alzheimer’s disease
Glutaminyl cyclase (QC) was discovered recently as the enzyme catalyzing the pyroglutamate (pGlu or pE) modification of N-terminally truncated Alzheimer’s disease (AD) Aβ peptides in vivo. This modification co...
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Article
Open AccessIntraneuronal pyroglutamate-Abeta 3–42 triggers neurodegeneration and lethal neurological deficits in a transgenic mouse model
It is well established that only a fraction of Aβ peptides in the brain of Alzheimer’s disease (AD) patients start with N-terminal aspartate (Aβ1D) which is generated by proteolytic processing of amyloid precurso...
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Article
Glutaminyl cyclase inhibition attenuates pyroglutamate Aβ and Alzheimer's disease–like pathology
Some Aβ peptides contain pyroglutamate modifications that affect the aggregation properties of these peptides. The authors find that the enzyme glutaminyl cyclase is responsible for this pyroglutamate modifica...
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BI-Einsatz bei Krankenversicherern
Die Neuaufteilung des Versicherungsmarktes ist in vollem Gange. Immer mehr Versicherte wechseln aus finanziellen Erwägungen in Betriebskrankenkassen, die deutlich mehr als 1 Million neue Mitglieder im Jahr gew...
