A5033223824- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Dementia and Cognitive Impairment Research
- Neuroscience and Neural Engineering
- Tuberous Sclerosis Complex Research
- Single-cell and spatial transcriptomics
- Electrochemical sensors and biosensors
- Mitochondrial Function and Pathology
- Ion Channels and Receptors
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- Microtubule and mitosis dynamics
- Biochemical Acid Research Studies
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- Genetic and Kidney Cyst Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Intracerebral and Subarachnoid Hemorrhage Research
BioMed X Institute
2018-2023
Harvard University
2020
Boston Children's Hospital
2020
Heidelberg University
2020
Abstract Tau is a microtubule-binding protein that can receive various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Hyperphosphorylation of tau linked to its aggregation the formation neurofibrillary tangles (NFTs), which are hallmark Alzheimer’s disease (AD). While more than 70 phosphorylation sites have been detected previously on NFT tau, studies oligomeric detergent-soluble in human...
In Alzheimer disease, Tau pathology is thought to propagate from cell throughout interconnected brain areas. However, the forms of released into interstitial fluid (ISF) in vivo during development Tauopathy and their pathological relevance remain unclear. Combining microdialysis biochemical analysis, we find that transgenic mice, human (hTau) present ISF truncated comprises at least 10 distinct fragments spanning entire protein. The fragmentation pattern similar across different models,...
Tuberous sclerosis complex (TSC) is a neurogenetic disorder that leads to elevated mechanistic targeting of rapamycin 1 (mTORC1) activity. Cilia can be affected by mTORC1 signaling, and ciliary deficits are associated with neurodevelopmental disorders. Here, we examine whether neuronal cilia in TSC. We show cortical tubers from TSC patients mutant mouse brains have fewer cilia. Using high-content image-based assays, demonstrate activity inversely correlates ciliation TSC1/2-deficient...
Abstract Background Human tauopathies including Alzheimer’s disease (AD) are characterized by alterations in the post-translational modification (PTM) pattern of Tau, which parallel formation insoluble Tau aggregates, neuronal dysfunction and degeneration. While PTMs on aggregated have been studied detail, much less is known about patterns soluble Tau. Furthermore, other than phosphorylation only come into focus recently still understudied. Soluble species likely responsible for spreading...
Store-operated Ca2+ entry (SOCE) through plasma membrane channel Orai1 is essential for many cellular processes. SOCE, activated by ER store-depletion, relies on the gating function of STIM1 Orai1-activating region SOAR ER-anchored Ca2+-sensing protein STIM1. Electrophysiologically, SOCE characterized as release-activated current (ICRAC). A major regulatory mechanism that prevents deleterious overload slow Ca2+-dependent inactivation (SCDI) ICRAC. Several studies have suggested a role...
Intraneuronal aggregates of the microtubule binding protein Tau are a hallmark different neurodegenerative diseases including Alzheimer's disease (AD). In these aggregates, is modified by posttranslational modifications such as phosphorylation well proteolytic cleavage. Here we identify novel cleavage site at aspartate 65 (D65) that specific for caspase-2. addition, show previously described D421 also efficiently processed caspase-2, and both sites cleaved in human brain samples....
Developing an in vitro platform to study neuron-oligodendrocyte interaction, particularly myelination, is essential understand aberrant myelination neuropsychiatric and neurodegenerative diseases. Here, we provide a controlled, direct co-culture protocol for human induced-pluripotent-stem-cell (hiPSC)-derived neurons oligodendrocytes on three-dimensional (3D) nanomatrix plates. We describe steps differentiate hiPSCs into cortical oligodendrocyte lineage cells 3D nanofibers. then detail the...
Alzheimer's Disease (AD) is the major cause of dementia in elderly, and cortical neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) can recapitulate disease phenotypes such as tau phosphorylation or amyloid beta (Aß) deposition. Here we describe generation an iPSC cohort consisting 2 sporadic AD cases 3 controls, derived dermal fibroblasts. All lines were karyotypically normal, showed expression cell markers efficiently into all three germ layers.
Abstract Tau is a microtubule-binding protein that can receive various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Hyperphosphorylation of tau linked to its aggregation the formation neurofibrillary tangles (NFTs), which are hallmark Alzheimer’s disease (AD). While more than 70 phosphorylation sites have been detected previously on NFT tau, studies oligomeric detergent-soluble in human...
One of the biggest challenges in field neurological disorders is limited availability freshly dissected human brain tissue. Therefore, use induced pluripotent stem cells (hiPSCs) important to develop brain-like models study interaction different cell types health and disease. For physiologically relevant disease modeling, three-dimensional (3D) culture systems are great importance because they provide a more representative vivo-like micro-environment cells. The 3D using diverse hiPSC-derived...
Abstract Background Tau cleavage by different proteolytic enzymes generates short, aggregation-prone fragments that have been implicated in the pathogenesis of Alzheimer’s disease (AD). Asparagine endopeptidase (AEP) activity particular has associated with tau dysfunction and aggregation, protease is increased both aging AD. Methods Results Using a mass spectrometry approach we identified novel site at N167 confirmed its processing AEP. In combination previously known N368, show AEP yields...
Abstract Human tauopathies including Alzheimer’s disease (AD) are characterized by alterations in the post-translational modification (PTM) pattern of Tau, leading to formation insoluble aggregates, neuronal dysfunction and degeneration. Using a mass spectrometry approach, we identified multiple sites lysine monomethylation on Tau isolated from detergent-soluble fraction human brain, some which were increased early AD samples. Brain tissues derived mouse model tauopathy demonstrate an...
Abstract In Alzheimer disease, Tau pathology is thought to propagate from cell throughout interconnected brain areas. However, the forms of released into interstitial fluid (ISF) in vivo during development Tauopathy and their pathological relevance remain unclear. Combining microdialysis biochemical analysis, we find that transgenic mice, human (hTau) present ISF truncated comprises at least 10 distinct fragments spanning entire protein. The fragmentation pattern similar across different...