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- Clinical Introduction
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1. Frontotemporal dementia
- Prof. Bruce Miller
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2. Parkinson disease
- Prof. Stanley Fahn
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3. Atypical parkinsonian syndromes
- Dr. David Burn
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4. Huntington's disease
- Prof. Roger Barker
- Neuroimaging
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5. Molecular brain imaging (PET) in diseases with dementia
- Prof. Karl Herholz
- Pathology, Genetic and Molecular Aspects (1)
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6. A molecular understanding of Alzheimer's disease
- Prof. John Hardy
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7. Neuropathology of neurodegenerative disorders
- Prof. Jillian Kril
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9. Ubiquitination and Alzheimer related disorders
- Prof. John Mayer
- Pathology, Genetic and Molecular Aspects (2)
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10. The molecular biology of Huntington's disease
- Prof. David C. Rubinsztein
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11. Metals, oxidative stress and neurodegeneration
- Prof. Ashley Bush
- Latest Developments in the Field
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12. Animal models of tauopathy
- Prof. David Westaway
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13. Parkinson's disease and transplants
- Prof. Roger Barker
- Archived Lectures *These may not cover the latest advances in the field
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14. Neuropathology of neurodegenerative disorders
- Prof. Jillian Kril
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15. Motor neurone disease: molecular basis
- Prof. Kevin Talbot
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16. Alzheimer's disease (AD)
- Prof. John Hodges
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17. Frontotemporal dementia syndromes
- Prof. John Hodges
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18. Motor neurone disease: clinical aspects
- Prof. Kevin Talbot
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19. Neuro-imaging in dementia: using MRI in routine work-up
- Prof. Philip Scheltens
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20. Prion diseases
- Prof. Pierluigi Gambetti
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21. Mitochondrial disorders and neurodegeneration
- Prof. Anthony Schapira
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23. Mutations in parkinsonian syndromes
- Dr. Andrew Singleton
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25. Frontotemporal dementia
- Prof. Bruce Miller
Printable Handouts
Navigable Slide Index
- Intro slide
- The brain is vulnerable to oxidative stress
- The chemistry of aging
- Metals in the brain
- Brain copper and iron rise in senescence
- Metals mediate oxidation damage
- Summary: Cu and Fe
- Amyloid plaques and tangles
- A-beta is cleaved from the APP
- Alzheimer's Disease beta-amyloid (A-beta)
- A-beta is a Cu/Zn metalloprotein
- Zn & Cu precipitate A-beta rapidly and reversibly
- Zinc, copper and iron in plaque
- Zinc in plaque
- Zinc and copper in the brain
- Zinc in neocortex - electromicrography
- Zinc transporter k/o inhibits A-beta deposition
- Synaptic zinc fosters CAA
- A-beta dimers in metal-chelated AD brain
- A-beta is redox active
- A-beta/Cu induces tyrosine radicals
- Cu mediates A-beta catalytic activity
- Peroxidative activity generates oxidized A-beta
- A-beta-COX2 adducts are elevated in AD
- Secondary consequences of H202 production
- Amyloid plaques and oxidative damage in AD
- Decreased Cu worsens amyloid
- Pleiotropic effects of Cu levels
- Does A-beta normally handle Cu?
- Cu/Zn-A-beta forms hexamers
- Cu accumulates in neurons lacking APP
- Model for Alzheimer pathogenesis
- Clioquinol
- Effect of clioquinol on transgenic mice 1
- Effect of clioquinol on transgenic mice 2
- Clioquinol restores metal homeostasis
- Effect of CQ upon ADAS-Cog
- Effect of CQ upon plasma A-beta levels
- Effect of CQ upon Zn levels
- 125I-CQ in human brain
- Copper-induced alpha-crystallin oxidation
- Cu deficiency (Menkes ATP7A)
- Iron trapping ameliorates MPTP
- Summary
Topics Covered
- Production of reactive oxygen species (ROS)
- Chemical origin
- Generic mechanism of protein and transition metal combination
- Pathological protein aggregates
- Toxic ROS generation
- Role in etiology and tissue specificity of agedependent neurodegenerative diseases
Links
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Therapeutic Areas:
Talk Citation
Bush, A. (2020, August 13). Metals, oxidative stress and neurodegeneration [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 30, 2024, from https://doi.org/10.69645/IQMQ3904.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Ashley Bush has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.