Live imaging anterograde axonal transport. Video depicts SynCav1-transfected primary neuron demonstrating anterograde movement (from soma to axonal growth cone). Neuronal cell bodies (i.e., soma) were plated in microfluidic chambers (Xona Microfluidics). Axons enter the microfluidic chamber microgroove at 3 days and project distal axon compartment by day 5 or 7 in vitro. Image was captured with an inverted immunofluorescence microscope system (Leica) using a 100X oil objective with a Charged coupled device (CCD) camera (Rolero-MGi Fast 1397). Image was provided by Dr. Matthew Pearn, Department of Anesthesia, UC San Diego (B.P. Head Laboratory).
SynCav1 Enhances Dendritic Arborization. Neurons transfected with SynCav1 exhibit increase expression of the dendritic marker MAP2 (microtubule associated protein 2, red). Cav-1 (white) is localizes to the soma and along dendritic shafts. Insets show Cav-1 localizing to dendritic spines. Image was provided by B.P. Head Laboratory at UCSD.
Cav-1 scaffolds Pre- and Post-synaptic proteins in Synaptic Membranes. (A) Caveolin-1 (Cav-1) scaffolding domain (CSD) is shown as an α-helix (amino acids 79–96) with Cav-1 oligomers composed of 7 monomers and an approximate diameter of 11 nm. This proposed heptamer forms because α-helical lateral interactions proximal to the cytofacial lipid bilayer give rise to a filamentous assembly 50 nm long. (B) Cav-1 localizes to pre-synaptic vesicles at the synaptic terminal and scaffolds synaptic receptors to the post-synaptic membrane. During disease, synaptic transmission decreases, while SynCav1 restores synaptic plasticity in setting of neuronal diseases.
3D Video Reconstruction of AAV-SynRFP-injected mouse brain. Video of hippocampal cell bodies and neuronal processes are identified by red fluorescence protein (RFP). The video highlights the neuron-targeted technology (synapsin-driven transgene), the broad transgene expression, and vector distribution with minimal dose. Image was captured and generated on a ZEISS Lightsheet Z.1microscope. Video was provided by Dr. Shanshan Wang, Department of Anesthesia, UC San Diego (B.P. Head Laboratory).
Alsop Louie Partners
ABSTRACT: Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons,Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preservemotor andcognitive function in the brain trauma setting is unknown.
Decreased expression of prosurvival and progrowth-stimulatory pathways, in addition to an environment that inhibits neuronal growth, contribute to the limited regenerative capacity in the central nervous system following injury or neurodegeneration. Membrane/lipid rafts, plasmalemmal microdomains enriched in cholesterol, sphingolipids, and the protein caveolin (Cav) are essential for synaptic development/stabilization and neuronal signaling.
Abstract A delicate interneuronal communication between pre- and postsynaptic membranes is critical for synaptic plasticity and the formation of memory. Evidence shows that membrane/lipid rafts (MLRs), plasma membrane microdomains enriched in cholesterol and sphingolipids, organize presynaptic proteins and postsynaptic receptors necessary for synaptic formation and signaling. MLRs establish a cell polarity that facilitates transduction of extracellular cues to the intracellular environment.
BACKGROUND: Studies in vitro demonstrate that neuronal membrane/lipid rafts (MLRs) establish cell polarity by clustering progrowth receptors and tethering cytoskeletal machinery necessary for neuronal sprouting. However, the effect of MLR and MLR-associated proteins on neuronal aging is unknown.
Biotech company CavoGene LifeSciences has licensed a novel investigational gene therapy from the University of California San Diego and brought the technology across the country to Cleveland, where the six-month-old firm will be headquartered.
CLEVELAND, Feb. 4, 2019 /PRNewswire/ -- CavoGene LifeSciences announced today the appointment of Scott J. Fisher, PhD as Chief Executive Officer. Dr. Fisher is a regenerative medicine expert who has previously led drug development and gene therapy clinical research of multiple regenerative therapies at early stage companies. CavoGene will be headquartered at the Global Center for Heath Innovation in Cleveland, Ohio.
GLEN BURNIE, Md., Oct. 23, 2018 /PRNewswire/ -- CavoGene LifeSciences has announced that it has licensed a novel investigational gene therapy for patients with neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), traumatic brain and spinal cord injury, and age-related cognitive decline. Currently, there is a large unmet medical need for these life-threatening conditions.
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