A5103132906- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Trace Elements in Health
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Nuclear Receptors and Signaling
- Amyotrophic Lateral Sclerosis Research
- Child Nutrition and Feeding Issues
- Crystallography and molecular interactions
- Prion Diseases and Protein Misfolding
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Conducting polymers and applications
- Neurological diseases and metabolism
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- Cellular transport and secretion
- Gastrointestinal motility and disorders
- Adenosine and Purinergic Signaling
- Congenital gastrointestinal and neural anomalies
- Wnt/β-catenin signaling in development and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- S100 Proteins and Annexins
- Medicinal Plants and Neuroprotection
- Signaling Pathways in Disease
Stanford University
2017-2018
The University of Melbourne
2008-2018
Florey Institute of Neuroscience and Mental Health
2013-2018
Institute of Molecular Biology and Biotechnology
2014
Czech Academy of Sciences, Institute of Biotechnology
2014
Mental Health Research Institute
2008-2013
Biotechnology Institute
2011
Brain circuits that modulate sociability Understanding the neural mechanisms mediate social reward has important societal and clinical implications. Hung et al. found release of neuropeptide oxytocin in ventral tegmental area brain increased prosocial behaviors mice (see Perspective by Preston). Optogenetic manipulation influenced a context-dependent manner. Oxytocin activity dopamine cells project to nucleus accumbens, another key node circuitry brain. Science , this issue p. 1406 ; see also 1353
Cognitive decline in Alzheimer's disease (AD) involves pathological accumulation of synaptotoxic amyloid-beta (Abeta) oligomers and hyperphosphorylated tau. Because recent evidence indicates that glycogen synthase kinase 3beta (GSK3beta) activity regulates these neurotoxic pathways, we developed an AD therapeutic strategy to target GSK3beta. The the use copper-bis(thiosemicarbazonoto) complexes increase intracellular copper bioavailability inhibit GSK3beta through activation Akt signaling...
Alzheimer's disease is an age-related neurodegenerative disorder with its toxicity linked to the generation of amyloid-β peptide (Aβ). Within Aβ sequence, there a systemic repeat GxxxG motif, which theoretical studies have suggested may be involved in both aggregation and membrane perturbation, processes that been implicated toxicity. We synthesized modified peptides, substituting glycine for leucine residues within motif (GSL peptides). These GSL peptides undergo β-sheet fibril formation at...
Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) humans and an expression level-dependent phenotype transgenic rodents. We show that oral treatment with therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper<sup>II</sup> [Cu<sup>II</sup>(atsm)] increased concentration of mutant SOD1 (SOD1G37R) ALS model mice, but paradoxically improved locomotor function survival mice. To determine why mice levels had phenotype, we...
J. Neurochem. (2011) 119 , 220–230. Abstract Impaired metal ion homeostasis causes synaptic dysfunction and treatments for Alzheimer’s disease (AD) that target ions have therefore been developed. The leading compound in this class of therapeutic, PBT2, improved cognition a clinical trial with AD patients. aim the present study was to examine cellular mechanism action PBT2. We show PBT2 induces inhibitory phosphorylation α‐ β‐isoforms glycogen synthase kinase 3 activity is dependent on...
Parkinson’s disease (PD) is a progressive, chronic characterized by dyskinesia, rigidity, instability, and tremors. The defined the presence of Lewy bodies, which primarily consist aggregated α-synuclein protein, accompanied loss monoaminergic neurons. Current therapeutic strategies only give symptomatic relief motor impairment do not address underlying neurodegeneration. Hence, we have identified CuII(atsm) as potential for PD. Drug administration to four different animal models PD resulted...
Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which an orally bioavailable, blood-brain barrier-permeable complex. In vitro compound inhibits action peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) subsequent nitration cellular proteins. Oral treatment transgenic SOD1G93A mice...
Brainwash! A platinum complex (see scheme) was developed that could be administered orally and reduce the amyloid burden in brains of transgenic mouse models suffering from Alzheimer's disease. Analyses brain tissues showed treatment with Pt compound led to a 26 % decrease number β-peptide plaques.
All cases of Huntington's disease (HD) are caused by mutant huntingtin protein (mhtt), yet the molecular mechanisms that link mhtt to symptoms not fully elucidated. Given glycogen synthase kinase-3 (GSK3) is implicated in several neurodegenerative diseases as a mediator neuronal decline and widely touted therapeutic target, we investigated GSK3 cells expressing mhtt, brains R6/1 HD mice post-mortem human brain samples. Consistency data across two models samples indicate decreased signalling...
Abstract Patients with Parkinson’s disease often experience non-motor symptoms including constipation, which manifest prior to the onset of debilitating motor signs. Understanding causes these deficits and developing modifying therapeutic strategies has potential prevent progression. Specific neuronal subpopulations were reduced within myenteric plexus mice 21 days after intoxication by intraperitoneal administration MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was associated a...
Tauopathies are characterized by the pathological accumulation of microtubule associated protein tau within brain. We demonstrate here that a copper/zinc chaperone (PBT2, Prana Biotechnology) has rapid and profound effects in rTg(tauP301L)4510 mouse model tauopathy. This was evidenced significantly improved cognition, preservation neurons, decrease aggregates other forms "pathological" (including phosphorylated sarkosyl-insoluble tau). Our data one primary mechanisms action PBT2 this may be...
Abstract The administration of MPTP selectively targets the dopaminergic system resulting in Parkinsonism-like symptoms and is commonly used as a mice model Parkinson’s disease. We previously demonstrated that neuroprotective compound Cu II (atsm) rescues nigral cell loss improves dopamine metabolism model. mechanism action needs to be further defined understand how promotes neuronal survival. Whole genome transcriptomic profiling has become popular method examine relationship between gene...
Alzheimer's disease is associated with the presence of insoluble protein deposits in brain called amyloid plaques. The major constituent these aggregated amyloid-β peptide. Technetium-99m complexes that bind to plaques could provide important diagnostic information on plaque burden using Single Photon Emission Computed Tomography (SPECT). Tridentate ligands a stilbene functional group were used form fac-[M(I)(CO)3](+) (M = Re or (99m)Tc) core. rhenium carbonyl tridentate co-ligands included...
Alzheimer's disease (AD) is the leading cause of dementia worldwide accounting for around 70% all cases. There currently no treatment AD beyond symptom management and attempts at developing disease-modifying therapies have yielded very little. These strategies traditionally targeted peptide Aβ, which thought to drive pathology. However, lack clinical translation these Aβ-centric underscores need diverse targeting other aspects disease. Metal dyshomeostasis a common feature several...
Parkinson's disease is diagnosed upon the presentation of motor symptoms, resulting from substantial degeneration dopaminergic neurons in midbrain. Prior to diagnosis, there a lengthy prodromal stage which non-motor including olfactory deficits (hyposmia), develop. There limited information about impairments and need for directed research into these early pathogenic cellular pathways that precede extensive death The protein tau has been identified as genetic risk factor development sporadic...
Gehirnwäsche! Ein Platin-Komplex (siehe Schema) wurde entwickelt, der oral gegeben werden kann und die Amyloid-Belastung in den Gehirnen transgener Mausmodelle mit Alzheimer-Krankheit reduziert. Analysen von Gehirngewebe zufolge führte Behandlung Pt-Verbindung zu einer 26 %-igen Verminderung Zahl an Amyloid-β-Peptid-Plaques.
Oligomeric forms of amyloid-β (Aβ) are thought to be responsible for the pathogenesis Alzheimer's disease. While many oligomers Aβ naturally occurring in brain humans and/or transgenic animals, it is well known that also readily produced vitro laboratory. In recent studies, we discovered synthetic monomeric (4.7 kDa) could transformed by microdialysis higher molecular weight species (approximately 56 kDa, western blot). Surface-enhanced laser desorption/ionization mass spectrometry and...