Research in the field of neuroscience has provided a better understanding of the cascade of biochemical events in neurodegenerative diseases. Most neurodegenerative conditions are marked by the presence of protein aggregations, and, in many cases, increased levels of oxidative damage in post-mortem tissues. The proteins associated with the neurodegenerative conditions may cause the over-production of free radicals in the neuronal tissues of the patients. We discovered that a 5-amino-acid sequence, Gly-Ala-Ile-Ile-Gly, residues 29 to 33 of the [beta]-amyloid protein from Alzheimer's disease, is also found in proteins from three neurodegenerative viruses: HIV-1, Newcastle disease virus, and Japanese encephalitis virus. We used PC12 cells and SH-SY5Y cells to study the toxicity of the peptide, using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium (MTT) assay and the measurement of caspase-3 activity.

1. ROLE OF FREE RADICALS IN
NEURODEGENERATIVE DISEASES
Presented by : Sapna Rani
MMCP,MMDU.

2. FREE RADICALS
• Chemical atoms and molecules which have
unpaired/single/odd number of electrons due
to loss of electron in outermost shell.
• Very dangerous as they are very reactive.
• Act as live bullets, roaming in body and
silently damaging our body’s vital organs.

3. Types of Free Radicals
• Free radicals of oxygen (Reactive oxygen
species (ROS).
• Examples:- Superoxide, Hydroxyl ions.
• Free radicals of nitrogen (RNS) like NO.
• Free radicals of sulphur like thiyl (RS) group.

4. Free Radicals of oxygen

5. Free Radicals of Nitrogen and Carbon

6. Free radicals formation

7. Radicals mediated cell damage

8. Role of Free Radicals
• Action on DNA
• Breaks, fragmentation of DNA strands
• Changes in DNA will change protein synthesis
• Leads to various disease and disorders
• Action on cell membrane integrity
• Cell death.

9. Contribution of Free Radicals in
neurodegenerative diseases
• Reactive oxygen metabolites play an
important role in the degeneration of brain
cells
• Free radicals cause gradual deterioration leads
to tissue injury.
• For most biological structures (like lipids,
proteins and nucleic acids) free radical
damage is closely associated with oxidative
damage, causing direct cellular injury.

10. Neurological disease and oxidative
stress
• Oxidative stress has been investigated in
neurological diseases including Alzheimer’s
disease, Parkinson’s disease, memory loss and
depression.
• Oxidative damage play a key role in the loss of
neurons and the progression to dementia.
• The production of beta-amyloid, a toxic peptide
often found present in Alzheimer’s patient brain,
is due to oxidative stress and plays an important
role in the neurodegenerative processes.

11. Neurodegenerative Diseases

12. Role of free radicals in
neurodegenerative disease
• Oxidative stress in the brain is likely to occur
as the brain uses up to 20 % of the body’s
inspired oxygen.
• The brain also houses large concentrations of
polyunsaturated fatty acids, which may
undergo lipid per-oxidation in such an oxygen
rich environment.
• ROS have been implicated in the pathology of
a number of neurological disorders.

13. Parkinson’s Disease
• Dopamine is metabolized in the cytosol and can
result in the production of hydrogen peroxide.
• Hydrogen peroxide can be converted to highly
reactive hydroxyl radicals which are extremely
toxic and can cause damage to dopaminergic
neurons.
• Increased lipid peroxidation, increased ROS
production and decreased levels of reduced
glutathione have been identified in the substantia
nigra of patients suffering from parkinson’s
disease.

14. SOD Role

15. Alzheimer’s disease
• AD is associated with loss of neurons due to
increased oxidative stress in the brain of the
patients.
• Decreased level of antioxidant, vitamin E and
C have also been associated with alzheimer
disease.

16. Free Radicals Formation

17. Role of free radicals and antioxidants
• Imbalance between free radicals formation and
defense mechanism of antioxidants leads to
serious neurodegeneration.
• Neuronal cells suffer functional or sensory loss in
neurodegenerative diseases.
• Toxicity of free radicals contributes to proteins
and DNA injury, inflammation, tissue damage.
• They are also involved in many biological
activities of cells such as signal transduction and
gene transcription.

18. Antioxidants role
• Oxygen related free radicals and reactive
species are produced in body and at the same
time antioxidants such as glutathione,
arginine, vitamin E and C regulate the ROS
thus generated.
• Antioxidant is further supported with
antioxidant enzymes, e.g. superoxide
dismutase, catalase, glutathione reductase in
removing free radicals.

19. Generation of ROS