9 documents found, page 1 of 1
Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and T...
Eira, J; Magalhães, J; Macedo, N; Pero, ME; Misgeld, T; Sousa, MM; Bartolini, F; Liz, MATransthyretin (TTR), a plasma and cerebrospinal fluid protein, increases axon growth and organelle transport in sensory neurons. While neurons extend their axons, the microtubule (MT) cytoskeleton is crucial for the segregation of functional compartments and axonal outgrowth. Herein, we investigated whether TTR promotes axon elongation by modulating MT dynamics. We found that TTR KO mice have an intrinsic incre...
The membrane periodic skeleton is an actomyosin network that regulates axonal d...
Costa, AR; Sousa, SC; Pinto-Costa, R; Mateus, JC; Lopes, CDF; Costa, AC; Rosa, D; Machado, D; Pajuelo, L; Wang, X; Zhou, FQ; Pereira, AJ; Sampaio, PNeurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain-and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active...
Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon I...
Costa, AR; Sousa, MMBy binding to actin filaments, non-muscle myosin II (NMII) generates actomyosin networks that hold unique contractile properties. Their dynamic nature is essential for neuronal biology including the establishment of polarity, growth cone formation and motility, axon growth during development (and axon regeneration in the adult), radial and longitudinal axonal tension, and synapse formation and function. In this...
Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in S...
Moreno, PM; Ferreira, AR; Salvador, D; Rodrigues, MT; Torrado, M; Carvalho, ED; Tedebark, U; Sousa, MM; Amaral, IF; Wengel, J; Pêgo, APAfter spinal cord injury (SCI), nerve regeneration is severely hampered due to the establishment of a highly inhibitory microenvironment at the injury site, through the contribution of multiple factors. The potential of antisense oligonucleotides (AONs) to modify gene expression at different levels, allowing the regulation of cell survival and cell function, together with the availability of chemically modified...
The Regulation of Axon Diameter: From Axonal Circumferential Contractility to A...
Costa, AR; Pinto-Costa, R; Sousa, S; Sousa, MMIn the adult nervous system axon caliber varies widely amongst different tracts. When considering a given axon, its diameter can further fluctuate in space and time, according to processes including the distribution of organelles and activity-dependent mechanisms. In addition, evidence is emerging supporting that in axons circumferential tension/contractility is present. Axonal diameter is generically regarded ...
Fibrin functionalization with synthetic adhesive ligands interacting with a6ß1 ...
Silva, J; Bento, AR; Barros, D; Laundos, TL; Sousa, SR; Quelhas, P; Sousa, MM; Pêgo, AP; Amaral, IFTo enhance fibrin hydrogel affinity towards pluripotent stem cell-derived neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration and neurite extension, we explored the tethering of synthetic peptides engaging integrin a6ß1, a cell receptor enriched in NSPCs. Six a6ß1 integrin ligands were tested for their ability to support integrin a6ß1-mediated adhesion of embryonic stem cell-derived ...
The actin-binding protein α-adducin is required for maintaining axon diameter
Leite, SC; Sampaio, P; Sousa, VF; Nogueira-Rodrigues, J; Pinto-Costa, R; Peters, LL; Brites, P; Sousa, MMThe actin-binding protein adducin was recently identified as a component of the neuronal subcortical cytoskeleton. Here, we analyzed mice lacking adducin to uncover the function of this protein in actin rings. a-adducin knockout mice presented progressive axon enlargement in the spinal cord and optic and sciatic nerves, followed by axon degeneration and loss. Using stimulated emission depletion super-resolution...
Peripheral nervous system plasmalogens regulate Schwann cell differentiation an...
Silva, TF; Eira, J; Lopes, AT; Malheiro, AR; Sousa, V; Luoma, A; Avila, RL; Wanders, RJ; Just, WW; Kirschner, DA; Sousa, MM; Brites, PRhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral ...
Deposition and passage of transthyretin through the blood-nerve barrier in reci...
Sousa, MM; Ferrão, J; Fernandes, R; Guimarães, A; Geraldes, B; Perdigoto, R; Tomé, L; Mota, O; Negrão, L; Furtado, AL; Saraiva, MJFamilial amyloid polyneuropathy (FAP) is characterized by deposition of mutated transthyretin (TTR) in the peripheral nervous system. Prior to amyloid fibrils, nonfibrillar TTR aggregates are deposited inducing oxidative stress with increased nitration (3-NT). As the major source of TTR is the liver, liver transplantation (LT) is used to halt FAP. Given the shortage of liver donors, domino LT (DLT) using FAP li...