A5073167752- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Neuroendocrine regulation and behavior
- Pancreatic function and diabetes
- Hormonal Regulation and Hypertension
- Diabetes Treatment and Management
- Neuroscience of respiration and sleep
- Nitric Oxide and Endothelin Effects
- Heart Failure Treatment and Management
- Protein Hydrolysis and Bioactive Peptides
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Stress Responses and Cortisol
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiovascular Function and Risk Factors
- Ion channel regulation and function
- Metabolism, Diabetes, and Cancer
- Apelin-related biomedical research
- Adenosine and Purinergic Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Neuroendocrine Tumor Research Advances
Monash University
2015-2024
Australian Regenerative Medicine Institute
2016-2024
Clayton Foundation
2020
Science for Life Laboratory
2016
Karolinska Institutet
1988-2016
Uppsala University
2016
The University of Melbourne
2002-2011
Florey Institute of Neuroscience and Mental Health
2001-2011
Université Paris Cité
2011
Vrije Universiteit Brussel
2011
Central infusion of angiotensin IV or its more stable analogues facilitates memory retention and retrieval in normal animals reverses amnesia induced by scopolamine bilateral perforant pathway lesions. These peptides bind with high affinity specificity to a novel binding site designated the AT(4) receptor. Until now, receptor has eluded molecular characterization. Here we identify receptor, protein purification peptide sequencing, be insulin-regulated aminopeptidase (IRAP). HEK 293T cells...
Abstract The role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4 + ) non-containing (XO4 − from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories ageing mice. microglial transcriptomes demonstrated dysregulated expression genes associated late onset AD. We further showed that the...
Presentation of exogenous antigens on MHC class I molecules, termed cross-presentation, is essential for the induction CD8 T-cell responses and carried out by specialized dendritic cell (DC) subsets. The mechanisms involved remain unclear. It has been proposed that could be transported endocytic receptors, such as mannose receptor (MR) in case soluble ovalbumin, into early endosomes which cross-presentation machinery would recruited. In these endosomal compartments, peptides trimmed...
Abstract Angiotensin IV (Ang IV) exerts profound effects on memory and learning, a phenomenon ascribed to its binding specific AT 4 receptor. However the receptor has recently been identified as insulin‐regulated aminopeptidase (IRAP). In this study, we demonstrate that ligands, including Ang IV, Nle 1 ‐Ang divalinal‐Ang structurally unrelated LVV‐hemorphin‐7, are all potent inhibitors of IRAP catalytic activity, assessed by cleavage leu‐β‐naphthylamide recombinant human IRAP. Both...
Abstract Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative vitro autoradiography. receptors labelled with antagonist analogue 125 I‐[Sar 1 , Ile 8 ] All while was I‐351A, a derivative of specific inhibitor, lisinopril. binding are present high concentrations nucleus solitary tract, dorsal motor vagus, rostral caudal ventrolateral reticular nucleus, band connecting ventral regions. In distributed punctate...
Approximately one-quarter of people over the age 65 are estimated to suffer some form cognitive impairment, underscoring need for effective cognitive-enhancing agents. Insulin-regulated aminopeptidase (IRAP) is potentially an innovative target development enhancers, as its peptide inhibitors exhibit memory-enhancing effects in both normal and memory-impaired rodents. Using a homology model catalytic domain IRAP virtual screening, we have identified class nonpeptide, small-molecule IRAP....
Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) has been reported to interact with specific high-affinity receptors increase memory retrieval, enhance dopamine-induced stereotypy behavior, and induce c-fos expression in several brain nuclei. We have isolated a decapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from sheep that binds high affinity the angiotensin receptor. The peptide was using 125I-angiotensin binding bovine adrenal membranes assay receptor activity. This is identical amino acid...
Abstract Background : Animal studies have demonstrated an interaction within the striatum between angiotensin and dopaminergic systems. In rats, converting enzyme (ACE) inhibitor, perindopril, crosses blood brain barrier increases striatal dopamine synthesis release. humans, type 1 receptors been found on neurons in substantia nigra striatum. Parkinson's disease, there is a marked reduction of these associated with nigrostriatal neuron loss. Aims We performed double blind placebo controlled...
Abstract: The effect of chronic inhibition the angiotensin‐converting enzyme on dopamine content and release in striatum was investigated using vivo microdialysis awake, freely moving rats. Rats were treated for 1 week with inhibitor perindopril (1 mg/kg) via drinking water, whereas controls given water alone. One after treatment, striatal dialysate levels group markedly elevated compared control values: control, 233 ± 43 pg/ml; perindopril, 635 53 pg/ml ( p < 0.001). These results...
In the human brain, receptor binding sites for angiotensin are found in striatum and substantia nigra pars compacta overlying dopamine-containing cell bodies. contrast, angiotensin-converting enzyme occurs reticulata is enriched striosomes of striatum. this study, using quantitative vitro autoradiography, we demonstrate decreased postmortem brains from patients with Parkinson's disease. same density to shows no consistent change. We propose, these results, that receptors located...
Abstract It is proposed that insulin‐regulated aminopeptidase (IRAP) the site of action two peptides, angiotensin IV and LVV‐hemorphin 7, which have facilitatory effects on learning memory. In fat muscles, IRAP codistributes with insulin‐responsive glucose transporter GLUT4 in specialised vesicles, where it plays a role tethering and/or trafficking these vesicles. This study investigated whether an analogous system exists functionally distinct regions brain, hippocampus cerebellum....
Abstract Insulin-regulated aminopeptidase (IRAP), a marker of glucose transporter 4 (GLUT4) storage vesicles (GSVs), is the only protein known to traffic with GLUT4. In basal state, GSVs are sequestered from constitutively recycling endosomal system an insulin-responsive, intracellular pool. Insulin induces rapid translocation cell surface this pool, resulting in incorporation IRAP and GLUT4 into plasma membrane. We sought identify proteins that interact further understand GSV trafficking...