A5020807285- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Axon Guidance and Neuronal Signaling
- Cholinesterase and Neurodegenerative Diseases
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipid Membrane Structure and Behavior
- Memory and Neural Mechanisms
- Neuroscience of respiration and sleep
- Cellular transport and secretion
- Neonatal Respiratory Health Research
- Sphingolipid Metabolism and Signaling
- Eicosanoids and Hypertension Pharmacology
- RNA Research and Splicing
- Dialysis and Renal Disease Management
- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Amino Acid Enzymes and Metabolism
- Biotin and Related Studies
- Prion Diseases and Protein Misfolding
- Erythropoietin and Anemia Treatment
The University of Melbourne
2009-2021
The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, therapeutic inhibition may cause unwanted adverse effects due to its additional functions the nervous system, such as myelination and neuronal connectivity. Additionally, recent proteomic studies investigating cell lines cultured murine neurons identified wider range of membrane proteins potential substrates, including seizure protein 6 (SEZ6) homolog SEZ6L. We generated antibodies...
Seizure-related gene 6 (Sez6), Sez6-Like (Sez6L), and 2 (Sez6L2) comprise a family of homologous proteins widely expressed throughout the brain that have been linked to neurodevelopmental psychiatric disorders. Here, we use Sez6 triple knockout (TKO) mice, which lack all three proteins, demonstrate regulate dendritic spine structure cognitive functions, motor learning, maintenance functions across lifespan. Compared WT controls, found TKO mice had impaired learning their coordination was...
The EphA4 receptor tyrosine kinase is a major regulator of axonal growth and astrocyte reactivity possible inflammatory mediator. Given that multiple sclerosis (MS) primarily an demyelinating disease in mouse models MS, such as experimental autoimmune encephalomyelitis (EAE), degeneration reactive gliosis are prominent clinical features, we hypothesised endogenous could play role modulating EAE. EAE was induced knockout wildtype mice using MOG peptide immunisation severity histological...
Mice lacking the axon guidance molecule EphA4 have been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which may modify response neural injury a microarray was performed on tissue from mice with sham injured controls. RNA purified cords of adult knockout wild-type four days lumbar hemisection or laminectomy only hybridised Affymetrix All-Exon Array 1.0 GeneChips™. While subsequent analyses indicated that several...
In order to demonstrate the cell-surface localization of a putative transmembrane receptor in cultured neurons, we labeled protein on surface live neurons with specific primary antibody raised against an extracellular portion protein. Given that receptors are trafficked and from surface, if cells permeabilized after fixation then both internal will be detected by same secondary antibody. Here, adapted method used study trafficking ("antibody feeding") differentially label had been...
Premature infants now have an improved chance of survival, but the impact respiratory therapies on brain, particularly cerebellum, remains unclear. We examined effects early nasal continuous positive airway pressure (EnCPAP) ventilation and delayed (Dn) CPAP development cerebellum in prematurely delivered baboons. The baboons were at 125 +/- 2days gestation ventilated for 28 days with either EnCPAP commencing 24 hours (n = 5) or DnCPAP 5 5). Gestational controls 4) 153 days. Cerebella...
In order to demonstrate the cell-surface localization of a putative transmembrane receptor in cultured neurons, we labeled protein on surface live neurons with specific primary antibody raised against an extracellular portion protein. Given that receptors are trafficked and from surface, if cells permeabilized after fixation then both internal will be detected by same secondary antibody. Here, adapted method used study trafficking ("antibody feeding") differentially label had been...
BACE inhibitors, which decrease BACE1 (β-secretase 1) cleavage of the amyloid precursor protein, are a potential treatment for Alzheimer's disease. Clinical trials using inhibitors have reported lack positive effect on patient symptoms and, in some cases, led to increased adverse events, cognitive worsening and hippocampal atrophy. A drawback this strategy is inhibition other substrates such as Seizure-related gene 6 (Sez6) family proteins known role neuronal function. Mice were treated with...
The membrane protein seizure 6-like (SEZ6L) is a neuronal substrate of the Alzheimer's disease protease BACE1, and little known about its physiological function in nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes adulthood, including changes gait decreased coordination. Additionally, displayed increased anxiety-like behaviour, although spatial learning memory Morris water maze were normal. Analysis gross anatomy proteome adult cerebellum did not...
Abstract Background BACE inhibitors, which decrease BACE1 (β-secretase 1) cleavage of the amyloid precursor protein, are a potential treatment for Alzheimer’s disease. Clinical trials using inhibitors have reported lack positive effect on patient symptoms and, in some cases, led to increased adverse events, cognitive worsening and hippocampal atrophy. A drawback this strategy is inhibition other substrates such as Seizure-related gene 6 (Sez6) family proteins known role neuronal function....