Paul-Flechsig-Institut für Hirnforschung
 Universitätsmedizin Leipzig

Pathogenic protein modifications

Signatures of modified Abeta peptides in brains of Alzheimer’s disease subjects revealed by novel monoclonal antibodies

In this project we will test the hypothesis that defined Abeta peptide variants contribute to the pathogenesis and progression of Alzheimer’s disease (AD) in a specific manner. Deposits of Abeta peptides in amyloid plaques are a histopathological hallmark of AD. Artikel lesen

Enzymatic regulation of CCL2 bioactivity in neuroinflammation

The present proposal focuses on the regulation of neuroinflammatory effects mediated by the C-C motif chemokine CCL2. We hypothesize that the biological activity of CCL2 for microglia/macrophage recruitment is tuned by enzyme-catalyzed post-translational modification. Artikel lesen

Contributions of glutaminyl cyclases to the pathogenesis of neurodegenerative disorders

This proposal is based on the hypothesis that a number of brain disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) share common pathogenic mechanisms leading to neurodegeneration. Artikel lesen

A novel mechanism for the modulation of brain immune cells

Immune cells of the brain play an important role in immune defense, removal of toxic substances and dead cells but also for proper neuronal function. Currently, a novel drug for the treatment of Alzheimer's disease is in clinical development. This drug inhibits the enzyme glutaminyl cyclase (QC), leading to the reduced formation of neurotoxic, pyroglutamate-modified Amyloid-beta peptides. Artikel lesen

Interaction von TDP-43- und Tau-Aggregation mit dem Mikrotubuli-Zytoskelett bei amyothropher Lateralsklerose

Protein aggregates with phosphorylated Transactivating Response Region (TAR) DNA Binding Protein (pTDP-43) have been identified in motor neurons of ALS patients as pathological hallmark. Artikel lesen

Are alpha-Synuclein fragments new substrates of glutaminyl cyclase?

The enzymatic activity of glutaminyl cyclase (QC) is required for the generation of highly neurotoxic variants of Abeta peptides in brains of Alzheimer’s disease patients. These pGlu-Abeta peptides resist proteolytical degradation, display a high aggregation velocity and co-aggregate unmodified Abeta peptides. Artikel lesen

Identification of substrates of the glutaminyl cyclases QC and isoQC

The development of inhibitors for the glutaminyl cyclases QC and isoQC is one of the most promising approaches for the treatment of Abeta pathology in Alzheimer’s disease (AD). Both enzymes, QC and isoQC, catalyse the intramolecular cyclization of N-terminal glutamine or glutamate residues of peptides into pyroglutamic acid (pGlu). This post-translationally modified Abeta was found to be the major constituent of Abeta plaques of AD patients. Artikel lesen

Cellular and molecular mechanisms of iso-glutaminyl cyclase-mediated neuroinflammatory diseases

The enzyme glutaminyl cyclase (QC) catalyzes the formation of N-terminal pyroglutamate (pGlu) residues on a number of neuropeptides, peptide hormones and chemokines. This modification reduces proteolytical degradation and thereby extends the biological efficacy of modified peptides. However, in Alzheimer's disease, pGlu-modified Abeta peptides with high neurotoxic properties were detected. Artikel lesen

Mechanisms of enzymatic cleavage of „Neural cell adhesion molecules“ (NCAM) by Prolyl Endopeptidase

The Junior Research Group MESCAMP investigates the enzyme prolyl endopeptidase (PREP) as player in the context of different psychiatric disorders, neurodegeneration and neuroinflammation. Artikel lesen
last update: 15.07.2020, 13:45 Uhr
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Paul-Flechsig-Institut für Hirnforschung