A5011681805- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Ubiquitin and proteasome pathways
- Botulinum Toxin and Related Neurological Disorders
- Tissue Engineering and Regenerative Medicine
- Histone Deacetylase Inhibitors Research
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Electrospun Nanofibers in Biomedical Applications
- Cell death mechanisms and regulation
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Lipid metabolism and biosynthesis
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
Boston Children's Hospital
2021-2025
Technical University of Munich
2022-2024
Max Planck Institute for Biological Intelligence
2022-2023
Max Planck Institute of Neurobiology
2019-2022
Max Planck Institute of Biochemistry
2022
Abstract Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization PTEN-induced kinase 1 (PINK1) requires transport Pink1 messenger RNA (mRNA) tethering it to the mitochondrial surface. Here, we report that inhibition AMP-activated protein (AMPK) activation insulin signalling cascade prevents mRNA binding mitochondria. Mechanistically, AMPK phosphorylates anchor complex subunit SYNJ2BP within its PDZ...
Motor axon regeneration following peripheral nerve injury is critical for motor recovery but therapeutic interventions enhancing this are not available. We conduct a phenotypic screen on human neurons and identified blebbistatin, non-muscle myosin II inhibitor, as the most effective neurite outgrowth promotor. Despite its efficacy in vitro, poor bioavailability limits vivo application. We, therefore, utilize blebbistatin analog, NMIIi2, to explore potential promoting regeneration. Local...
Abstract A central role in mitochondrial quality control is played by the Parkinson-related kinase PINK1, whose mRNA transported neurons hitch- hiking. Using a live-cell imaging assay for translation of PINK1 precursor, we show that local requires concerted interplay between mitochondria and ER neurons. For efficient translation, Pink1 needs to relocate ribosomes located near endolysosomes ER. The membrane-tethered chaperone DNAJB6 then shields precursor on transit following ER-SURF pathway....
Abstract Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization PTEN-induced kinase 1 (PINK1) requires transport Pink1 mRNA tethering it to the mitochondrial surface. Here, we report that inhibition AMPK activation insulin signaling cascade prevents binding mitochondria. Mechanistically, phosphorylates RNA anchor complex subunit SYNJ2BP within its PDZ domain, a phosphorylation site necessary for...
Summary CNS neurons do not regenerate after injury, leading to permanent functional deficits. Although sensory and motor neuron axons regrow peripheral nerve outcome is limited due the incomplete slow regrowth. The lack of human-relevant assays suitable for large-scale drug screens has neuro-repair therapy discovery. To address this we developed a phenotypic screening strategy using human induced pluripotent stem cell-derived identify axon-regeneration promoting compounds targets. involve...
Abstract PTEN-induced kinase 1 (PINK1) is a very short-lived protein that required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because short half-life PINK1 limits its ability to be trafficked into neurites, local translation this mitophagy pathway active far from soma. The Pink1 transcript associated with cotransported neuronal mitochondria. In concert translation, mitochondrial outer membrane Synaptojanin 2 binding (SYNJ2BP) (SYNJ2) are tethering...
<title>Abstract</title> Motor axon regeneration following peripheral nerve injury is critical for motor recovery but therapeutic interventions enhancing this are not available. We conducted a phenotypic screen on human neurons and identified blebbistatin, non-muscle myosin II inhibitor, as the most effective neurite outgrowth promotor. Despite its efficacy in vitro, poor bioavailability limits vivo application. We, therefore, utilized blebbistatin analog, NMIIi2, to explore potential...
Mitochondria are not only the “power houses of cell” but also function as a major Ca2+ buffer in cell. Mitochondrial dynamics respond to level cell order maintain beneficial feedback cycle between buffering and mitochondrial that allows adaption cellular (sub) environment. Mutations proteins linked Parkinson’s disease (PD) well both dysfunction dysregulation, which can trap vicious cycle.