A5005145881- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
- Cholinesterase and Neurodegenerative Diseases
- Nicotinic Acetylcholine Receptors Study
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Nuclear Receptors and Signaling
- Computational Drug Discovery Methods
- Drug Transport and Resistance Mechanisms
- Prion Diseases and Protein Misfolding
- Nerve injury and regeneration
- Protease and Inhibitor Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Signaling Pathways in Disease
- Immune cells in cancer
- Tryptophan and brain disorders
- Amino Acid Enzymes and Metabolism
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- 14-3-3 protein interactions
Leipzig University
2016-2025
Max Planck Institute for Human Cognitive and Brain Sciences
2023
Allen Institute for Brain Science
2020
Paul Drude Institute for Solid State Electronics
2007
KU Leuven
2005-2006
University of Bonn
2006
Universitätsklinikum Erlangen
2006
In-Q-Tel
2004
Epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the risk for Alzheimer's disease (AD). Certain NSAIDs can activate peroxisome proliferator-activated receptor-γ (PPARγ), which is a nuclear transcriptional regulator. Here we show PPARγ depletion potentiates β-secretase [β-site amyloid precursor protein cleaving enzyme (BACE1)] mRNA levels by increasing BACE1 gene promoter activity. Conversely, overexpression of PPARγ, as well and activators,...
Large amounts of adenosine 5′-triphosphate (ATP) released from cellular sources under pathological conditions such as ischemia may activate purinoceptors the P2X and P2Y types. In present study, expression P2X7 receptor-subtype in brain cortex spontaneously hypertensive rats was investigated using a permanent focal cerebral model. Immunocytochemistry with antibodies raised against intracellular C-terminus receptor showed time-dependent upregulation labeled cells peri-infarct region after...
Abstract The brains of Alzheimer's disease (AD) patients display cerebrovascular and parenchymal deposits β‐amyloid (Aβ) peptides, which are derived by proteolytic processing the β‐site APP‐cleaving enzyme 1 (BACE1) amyloid precursor protein (APP). rat BACE1 promoter has a nuclear factor‐κB (NF‐κB) binding site. Deletion studies with promoter/luciferase reporter suggest that NF‐κB DNA consensus sequence plays suppressor role, when occupied NF‐κB, in regulation neuronal brain expression. Here...
Brains of Alzheimer's disease (AD) patients are characterized in part by the formation high molecular weight aggregates amyloid-β (Aβ) peptides, which interfere with neuronal function and provoke cell death. The pyroglutamate (pGlu) modification Aβ was demonstrated to be catalyzed enzyme glutaminyl cyclase (QC) enhance pathogenicity neurotoxicity. Here, we addressed role QC AD pathogenesis human cortex. Two sets postmortem brain tissue from a total 13 non-demented controls 11 cases were...
Abstract Introduction In Alzheimer's disease (AD), pathologic amyloid‐beta (Aβ) is synaptotoxic and impairs neuronal function at the microscale, influencing brain networks macroscale before Aβ deposition. The latter can be detected noninvasively, in vivo , using resting‐state functional MRI (rsfMRI), a technique used to assess connectivity (FC). Methods RsfMRI was performed longitudinally TG2576 PDAPP mice, starting deposition determine earliest FC changes. Additionally, role of on early...
Transgenic animal models are invaluable research tools for elucidating the pathways and mechanisms involved in development of neurodegenerative diseases. Mechanistic clues can be revealed by applying labelling techniques such as immunohistochemistry or situ hybridisation to brain tissue sections. Precision both assigning anatomical location sections quantifying labelled features is crucial output validity, with a stereological approach image-based feature extraction typically used. However,...
Abstract The beta‐site APP‐cleaving enzyme (BACE1) is a prerequisite for the generation of β‐amyloid peptides, which give rise to cerebrovascular and parenchymal deposits in brain Alzheimer's disease patients. BACE1 neuronally expressed brains humans experimental animals such as mice rats. In addition, we have recently shown that protein by reactive astrocytes close proximity plaques aged transgenic Tg2576 overexpress human amyloid precursor carrying double mutation K670N‐M671L. To address...
Beta-amyloid (Abeta) peptides that accumulate in Alzheimer disease are generated from the beta-amyloid precursor protein (betaAPP) by cleavages beta-secretase BACE1 and presenilin-dependent gamma-secretase activities. Very few data document a putative cross-talk between these proteases regulatory mechanisms underlying such interaction. We show presenilin deficiency lowers maturation affects both activity promoter transactivation. The specific inhibitor DFK167 triggers decrease of wild-type...
Posttranslational amyloid-β (Aβ) modification is considered to play an important role in Alzheimer's disease (AD) etiology. An N-terminally modified Aβ species, pyroglutamate-amyloid-β (pE3-Aβ), has been described as a major constituent of deposits specific human AD but absent normal aging. Formed via cyclization truncated species by glutaminyl cyclase (QC; QPCT) and/or its isoenzyme (isoQC; QPCTL), pE3-Aβ aggregates rapidly and known seed additional aggregation. To directly investigate...
Alzheimer’s disease (AD) and Parkinson’s (PD), including dementia with Lewy bodies (DLB), account for the majority of cases worldwide. Interestingly, a significant number patients have clinical neuropathological features both AD PD, i.e., presence amyloid deposits in neocortex. The identification α-synuclein peptides plaques DLB brain led to hypothesis that mutually interact each other facilitate neurodegeneration. In this article, we report influence Aβ(1–42) pGlu-Aβ(3–42) on aggregation...
Synaptic dysfunction caused by soluble β-amyloid peptide (Aβ) is a hallmark of early-stage Alzheimer's disease (AD), and tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity cAMP-responsive element-binding protein (CREB), master regulator cell survival plasticity-related gene expression. Here, we report that elicits nucleocytoplasmic trafficking Jacob, connects NMDA-receptor-derived signalosome CREB, in AD patient brains mouse hippocampal...
Abstract We measured tissue distribution and expression pattern of the beta‐site amyloid precursor protein (APP)‐cleaving enzyme (BACE) in brains transgenic Tg2576 mice that show pathology. BACE was expressed at high levels brain; lower heart liver; very low pancreas, kidney, thymus almost absent spleen lung when assayed by Western blot analysis. observed strictly neuronal nontransgenic control mice, with most robust immunocytochemical labeling present cerebral cortex, hippocampal formation,...
Abstract For a long time, prolyl endopeptidase (PEP) was believed to inactivate neuropeptides in the extracellular space. However, reports on intracellular activity of PEP suggest additional, as yet unidentified, physiological functions for this enzyme. Here, we demonstrate using biochemical methods subcellular fractionation, immunocytochemical double‐labelling procedures and localization PEP–enhanced green fluorescent protein fusion proteins that is mainly localized perinuclear space,...
Abstract Permanent middle cerebral artery occlusion (MCAO) causes neurodegeneration and a robust activation of glial cells primarily in sensorimotor brain regions rats. It has been shown that hyperbaric oxygen (HBO) increases supply to ischaemic areas reduces neuronal cell loss. The effects HBO treatment on microgliosis astrogliosis permanent ischaemia have not addressed so far, but might be critical for neuroprotection, respectively. Therefore, we used spontaneously hypertensive rats with...
The upregulation of extracellular matrix components, especially chondroitin sulfate proteoglycans, after brain injury and stroke is known to accompany the glial reaction, forming repellent scars that hinder axonal growth reorganization injured neuronal networks. associated with perineuronal nets (PNs) in primarily remote regions has not yet been systematically analyzed. We use model permanent middle cerebral artery occlusion (MCAO) investigate acute long-lasting consequences ischemia for...
Abstract The β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β‐amyloid peptides, principle constituents senile plaques in brains patients with Alzheimer's disease (AD). BACE1 expression and enzymatic activity are increased AD brain, but regulatory mechanisms largely unknown. Here we show that Yin Yang (YY1), highly conserved multifunctional transcription factor, binds to its putative recognition sequence within promoter stimulates rat...
Abstract The aim of this study was to characterize the effects cortical cholinergic denervation on parameters in cerebral cortex and basal forebrain using a novel immunotoxin (conjugate monoclonal antibody 192IgG against low‐affinity nerve growth factor receptor armed with cytotoxin saporin) efficiently selectively lesion neurons rat forebrain. Seven days following an intracerebroventricular injection 192IgG‐saporin binding levels nicotinic M 1 ‐ 2 ‐muscarinic acetylcholine receptors...