A5102866719- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Lysosomal Storage Disorders Research
- Neurological Disease Mechanisms and Treatments
- S100 Proteins and Annexins
- Cellular transport and secretion
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Cerebrovascular and genetic disorders
- Signaling Pathways in Disease
- Intracerebral and Subarachnoid Hemorrhage Research
- Gut microbiota and health
- Adenosine and Purinergic Signaling
- Cholinesterase and Neurodegenerative Diseases
- Autoimmune Neurological Disorders and Treatments
- Biochemical and Molecular Research
- 14-3-3 protein interactions
- Plant-based Medicinal Research
- Neurological Complications and Syndromes
- Chemical Synthesis and Analysis
- SARS-CoV-2 and COVID-19 Research
- Hemophilia Treatment and Research
German Center for Neurodegenerative Diseases
2011-2024
University of Milan
2005-2023
Luigi Sacco Hospital
2022-2023
A. O. Ordine Mauriziano di Torino
2022
Technical University of Munich
2012-2016
Bayer (Italy)
2016
Klinikum rechts der Isar
2016
Sine Institute
2012
Ludwig-Maximilians-Universität München
2010-2012
Mario Negri Institute for Pharmacological Research
2006-2011
Abstract ATP has been indicated as a primary factor in microglial response to brain injury and inflammation. By acting on different purinergic receptors 2, is known induce chemotaxis stimulate the release of several cytokines from these cells. The activation 2 microglia can be triggered either by deriving dying cells, at sites or released astrocytes, absence cell damage. use biochemical approach integrated with video microscopy experiments, we investigated functional consequences...
Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, mechanisms microbiome–brain interaction AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) mice exhibit substantially reduced plaque load and markedly SCFA plasma concentrations; conversely, supplementation to GF increased levels conventionally colonized...
Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One proteases is a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase Alzheimer's disease amyloid precursor protein. ADAM10 also required for neuronal network functions murine brain, but substrates are only partly known. With a proteomic analysis Adam10-deficient neurons we identified 91, mostly novel substrate candidates, making protease proteins...
Alzheimer's disease (AD) is a major clinical concern, and the search for new molecules to combat progression remains important. One of hallmarks in AD pathogenesis hyperphosphorylation tau subsequent formation neuro
Proteolytic shedding of cell surface proteins generates paracrine signals involved in numerous signaling pathways. Neuregulin 1 (NRG1) type III is myelination the peripheral nervous system, for which it requires proteolytic activation by proteases ADAM family and BACE1. These are major therapeutic targets prevention Alzheimer's disease because they also generation neurotoxic amyloid β-peptide. Identification functional investigation their physiological substrates therefore greatest...
Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little known about proteome-wide changes in microglia during the course AD and their functional consequences. Here, we performed an in-depth time-resolved proteomic characterization two mouse models amyloid β (Aβ) pathology, overexpression APPPS1 knock-in APP-NL-G-F (APP-KI) model. We identified large panel Aβ Response Proteins (MARPs) that reflect heterogeneity microglial alterations early, middle advanced...
Abstract Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in NPC1 , resulting abnormal late endosomal/lysosomal lipid storage. Although microgliosis prominent pathological feature, direct consequences of loss on microglial function remain not fully characterized. We discovered proteomic signatures and phenotypes NPC1-deficient murine models demonstrate cell autonomous microglia. Loss triggers enhanced phagocytic uptake impaired myelin turnover...
Article12 September 2016Open Access Source DataTransparent process TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons Benjamin M Schwenk German Center for Neurodegenerative Diseases (DZNE), Munich, Germany Munich Cluster Systems Neurology (SyNergy), Search more papers by this author Hannelore Hartmann Alperen Serdaroglu Institute Advanced Study, Technische Universität München, Martin H Schludi Daniel Hornburg Max Planck Biochemistry, Martinsried,...
Abstract Microglia, glial cells with an immunocompetent role in the CNS, react to stimuli from surrounding environment alterations of their phenotypic response. Amongst other activating signals, endotoxin lipopolysaccharide (LPS) is widely used as a tool mimic bacterial infection CNS. LPS‐activated microglia undergo dramatic changes cell morphology/activity; particular, they stop proliferating and differentiate resting effector cells. Activated also show modifications purinoreceptor...
ATP is the main transmitter stored and released from astrocytes under physiological pathological conditions. Morphological functional evidence suggest that besides secretory granules, lysosomes release ATP. However, molecular mechanisms involved in astrocytic lysosome fusion remain still unknown.In present study, we identify tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP, also called VAMP7) as vesicular SNARE which mediates exocytosis, contributing to of both...
The neuropathological hallmarks of Alzheimer's disease (AD) are extracellular plaques built up by the accumulation amyloid-β protein precursor (AβPP)-derived peptide β (Aβ), and intracellular tangles hyperphosphorylated tau protein. Sirtuin 2 (SIRT2) is a member sirtuin family, fea turing conserved enzymes with deacetylase activity involved in several cell molecular pathways. We investigated importance SIRT2 inhibition AD. inhibited small molecules (AGK-2, AK-7) examined AβPP metabolism...
Abstract Introduction Murine microglia expressing the Alzheimer's disease–linked TREM2 R47H mutation display variable decrease in phagocytosis, while impaired phagocytosis is reported following loss of TREM2. However, no data exist on +/R47H human microglia. Therefore, we created pluripotent stem cell (hPSC) monocytes and transdifferentiated microglia‐like cells (tMGs) to examine effect phagocytosis. Methods We generated isogenic , +/− −/− hPSCs using CRISPR/Cas9. Following differentiation...
Alzheimer disease (AD) is characterized by cognitive impairment that starts with memory loss to end in dementia. Loss of synapses and synaptic dysfunction are closely associated AD patients. Biochemical pathological evidence suggests soluble Aβ oligomers correlate impairment. Here, we used the TgCRND8 mouse model investigate role JNK long term deficits. mice were chronically treated cell-penetrating c-Jun N-terminal kinase inhibitor peptide (D-JNKI1). D-JNKI1, preventing action, completely...
We describe here an innovative, non-transgenic animal model of Alzheimer's disease. This mimics early stages sporadic disease, which represents the vast majority cases. The was obtained by interfering with complex between a disintegrin and metalloproteinase domain containing protein 10 (ADAM10), main α-secretase candidate, its partner, synapse-associated 97, postsynaptic density-membrane associated guanylate kinase family. Association ADAM10 97 governs enzyme trafficking activity at...
The therapeutic efficacy of oncolytic viral therapy often comes as a tradeoff with safety, such that potent vectors are associated toxicity, while safer viruses tend to have attenuated effects. Despite promising preclinical data, the development VSV clinical agent has been substantially hampered by fact severe neurotoxicity and hepatotoxicity observed in rodents nonhuman primates response treatment wild-type VSV. Although NDV shown an attractive safety profile humans effects, its further...
Regulated intramembrane proteolysis of the amyloid precursor protein (APP) by protease activities α-, β- and γ-secretase controls generation neurotoxic β peptide. APLP2, precursor-like 2, is a homolog APP, which shows functional overlap with but lacks an domain. Compared to less known about proteolytic processing in particular neurons, cleavage sites have not yet been determined. APLP2 cleaved β-secretase BACE1 additionally α-secretase activity. The two metalloproteases ADAM10 ADAM17...