A5036111826- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Folate and B Vitamins Research
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- Calpain Protease Function and Regulation
- Cancer-related Molecular Pathways
- Axon Guidance and Neuronal Signaling
- Retinal Development and Disorders
- Biomarkers in Disease Mechanisms
- MicroRNA in disease regulation
- GDF15 and Related Biomarkers
- PI3K/AKT/mTOR signaling in cancer
- Traumatic Brain Injury and Neurovascular Disturbances
- Paraquat toxicity studies and treatments
- Glaucoma and retinal disorders
- Amyotrophic Lateral Sclerosis Research
- Neurological Disease Mechanisms and Treatments
- Organoselenium and organotellurium chemistry
- Signaling Pathways in Disease
- Bone Metabolism and Diseases
- Ocular Oncology and Treatments
Columbia University
2003-2024
Carleton University
2013-2023
University of Cambridge
2015-2016
Boston Children's Hospital
2008-2009
Harvard University
2008-2009
University of Ottawa
2001-2005
University of Pittsburgh
2003
The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration vivo. To test the role intrinsic impediments regrowth, we analyzed cell growth control genes using virus-assisted vivo conditional knockout approach. Deletion PTEN (phosphatase and tensin homolog), negative regulator mammalian target rapamycin (mTOR) pathway, adult retinal ganglion cells...
Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used targeting generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in substantia nigra fiber densities dopamine levels striatum normal. However, DJ-1–/– hypolocomotion when subjected amphetamine challenge increased striatal denervation dopaminergic loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine....
Recent evidence indicates that cyclin-dependent kinases (CDKs, cdks) may be inappropriately activated in several neurodegenerative conditions. Here, we report cdk5 expression and activity are elevated after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin damages the nigrostriatal dopaminergic pathway. Supporting pathogenic significance alterations findings general cdk inhibitor, flavopiridol, or dominant-negative cdk5, to lesser extent cdk2, attenuates loss...
Growing evidence implicates microglia in the loss of dopaminergic neurons Parkinson's disease (PD). However, factors mediating microglial activation PD are poorly understood. Proinflammatory cytokines, such as interferon-γ (IFN-γ), orchestrate actions microglia. We report here that patients express significantly elevated levels IFN-γ their blood plasma. After this initial finding, we found IFN -γ-deficient mice displayed attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced...
The molecular mechanisms mediating degeneration of midbrain dopamine neurons in Parkinson's disease (PD) are poorly understood. Here, we provide evidence to support a role for the involvement calcium-dependent proteases, calpains, loss mouse model PD. We show that administration N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes an increase calpain-mediated proteolysis nigral vivo. Inhibition calpain using either inhibitor (MDL-28170) or adenovirus-mediated overexpression endogenous...
The mechanisms underlying dopamine neuron loss in Parkinson's disease (PD) are not clearly defined. Here, we delineate a pathway by which dopaminergic induced 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) is controlled vivo . We reported previously that calpains play central required role after MPTP treatment. provide evidence the downstream effector of through cyclin-dependent kinase 5 (cdk5)-mediated modulation transcription factor myocyte enhancer 2 (MEF2). show MPTP-induced...
Accumulating evidence suggests that apoptotic and inflammatory factors contribute to the demise of dopaminergic neurons. In this respect, Fas, a member tumor necrosis factor receptor family with proapoptotic functions, was reported be elevated within striatum substantia nigra pars compacta (SNc) Parkinson's disease (PD) patients. Accordingly, present investigation evaluated function Fas in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model PD. Injection MPTP increased nigral...
Article17 June 2020Open Access Transparent process PI 3-kinase delta enhances axonal PIP3 to support axon regeneration in the adult CNS Bart Nieuwenhuis orcid.org/0000-0002-2065-2271 John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University Cambridge, UK Laboratory Regeneration Sensorimotor Systems, Netherlands Institute Neuroscience, Royal Academy Arts and Sciences (KNAW), Amsterdam, The Search more papers by this author Amanda C Barber Rachel S Evans Craig...
Expression of the transcription factor c-Jun is induced in neurons central nervous system (CNS) response to injury. Mechanical transection nigrostriatal pathway at medial forebrain bundle (MFB) results delayed retrograde degeneration dopamine substantia nigra pars compacta (SNc) and induces protracted expression phosphorylation c-Jun. However, role after axotomy CNS unclear. Here, we show that adenovirus-mediated a dominant negative form (Ad.c-JunDN) inhibited axotomy-induced neuron death...
Abstract Clinical stroke usually results from a cerebral ischaemic event, and is frequently debilitating condition with limited treatment options. A significant proportion of clinical strokes result specific damage to the subcortical white matter ( SWM ), but currently there are few animal models available investigate pathogenesis potential therapeutic strategies promote recovery. Granulocyte macrophage colony‐stimulating factor GM ‐ CSF ) cytokine that has been previously shown...
Lack of regeneration in the adult central nervous system (CNS) is a major hurdle that limits recovery from neurological ailments. Although accumulating research suggests possibility axon by targeting intrinsic signaling mechanisms, it remains matter controversy whether functional can be achieved manipulating aspects molecular signaling. Recent studies have shown granulocyte macrophage colony‐stimulating factor (GM‐CSF) may an effective means repair following CNS injury; how this molecule...
The prevalence of stroke increases with age and the ability to absorb all nutrients from our diets decreases age. Nutrition is a modifiable risk factor for stroke, which leading cause death disability in world-wide. Deficiencies one‑carbon metabolism, including methyltetrahydrofolate reductase (MTHFR), have been linked increased stroke. Mthfr+/− mice mouse model mimic phenotype MTHFR677C➔T polymorphism, such as elevated levels homocystine. Using this model, aim study was investigate impact...