![]() ![]() Axons could grow in 3D between different layers of the scaffold and extended along the fibers with a high degree of alignment to the pattern of the nanogrid, as opposed to the lack of directionality observed on flat glass or polymeric surfaces ( Figure 1). We characterized the physical and chemical properties and proved the biocompatibility of said scaffolds by successfully culturing primary sensory and motor neurons on their surface. We took advantage of state-of-the-art 2-photon photolithography to fabricate highly ordered and biocompatible 3D nanogrid structures to enhance neuronal directional growth. We will perform a proteomic and transcriptomic analysis this coming year to better elucidate the mechanisms behind neurodegeneration in human MNs.įinally, we aimed to deploy fibrous 3D scaffold/implants for the directed growth of axons, to restore and repair lost neuronal connections. In 2021 we have continued to characterize the hallmark of disease progression in these MNs and collect samples. Last year we established a differentiation protocol for human pluripotent stem cells (iPSC) into MNs. To overcome the limitations of murine models, we directly derive motor neurons (MNs) from ALS patient’s fibroblasts to assess how local mechanisms of protein production (translation) is changed in motor cells from ALS patients. ![]() We investigate what drives the rate of progression of neurodegeneration looking at a paradigm of fatal neurodegenerative disorders: Amyotrophic Lateral Sclerosis (ALS). We are also focused on strategies to promote axonal regeneration through to use of specialized substrates and the tools we have developed to investigate the mechanisms underlying axonal degeneration. We are now in the process of characterizing the most promising candidates in vitro and in vivo and their potential implication in the genesis of neurological disorders. We heave infected DRG neurons with our fusion constructs and performed a proteomic screen to identify DYNLRB1 interactors. To this extent we created several fusion constructs of DYNLRB1 and a promiscuous biotinylating enzyme to selectively label DYNLRB1’s interactors and identify them by mass spectrometry. We have been focusing on the interactors of a Dynein subunit, which is critical for the survival of sensory neurons (Terenzio et al., 2020). Anterograde and retrograde axonal transport is supported by various molecular motors, such as kinesins and dyneins, and a complex microtubule network. Axonal transport plays a central role in the establishment of neuronal polarity, axonal growth and stabilization and synapses formation, allowing for precise spatio-temporal activation and modulation of numerous molecular cascades. To maintain neuronal homeostasis, neurons rely extensively on axonal transport of membranous organelles and other molecular complexes in addition to local translation of proteins. Neurons are highly polarized cells with an elongated axon that extends far away from the cell body.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |