ROLE OF FREE RADICALS IN NEURODEGENERATIVE DISEASES ppt (2) (2).pptx

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