Neurodegenerative Diseases in Human and Animals

PRIONS

Muslima P. LiwalugMIB 1

ABSTRACT

PrPSc are infectious proteins that cause neurodegenerative diseases in humans and animals. Checking the signs of the disease is the best preliminary diagnosis and brain scan or blood test will determine the abnormal proteins that are present in the patient’s body. The result of the study determine the different kinds of neurodegenerative diseases that caused by PrPSc and how it affect the human and animals.

OBJECTIVESoTo determine Prions

oTo differentiate PrPC from PrPSc

oTo determine how it affects human and animal brains and the formation of holes

oTo determine the list of human and animal neurodegenerative diseases caused by PrPSc

PRIONS

o are not made up of cell

o proteins that are found

mostly abundant in the

brain

o doesn’t use energy

o doesn’t grow

o prions don’t die

o they reproduce via pre-

existing prions

ORIGIN OF PRIONS

All mammals appear to have prion protein genes and the gene sequences are similar, but not identical, in related species.

FUNCTION OF PRIONS

obinds with Cu (Copper)oAnti-oxidant activityoResistant to oxidative stressoPrevent neuronal dysfunction

oAbnormality of prion proteins can induce apoptosis of neurons.!

MATERIALS & METHODSChecking the List of

Signs of the Disease

Brain Scan via MRI or

EEG

Interpretation of the

Result

Blood Test

Interpretation of the

Result

SIGNS

Early Signs• Depression / anxiety• Insomnia• Dizziness• Altered mood• Unusual behavior• Tingling part of the

body

Later signs• Develops dementia• Loss of coordination• Visual disturbance

PS: Typical signs may not be present but problems with thinking skills or balance will certainly be noted.

BRAIN SCANS

Magnetic Resonance Imaging (MRI)

• reveals the characteristics patterns of brain degeneration that help diagnose PrPSc

Electroencephalogram (EEG)

• record the brain’s electrical pattern which can be particularly valuable because it shows specific type of abnormality in prion proteins

BLOOD TEST

Small amount of blood is mixed with special metal beads to which the PrPSc

sticks tightly.

Washed to removed PrPC and other blood components that could interfere with the test.

The amount of PrPSc attached to the beads is measured using newly developed antibodies that bind tightly to the prion proteins.

RESULTS

Click icon to add picture

Objectives:

TRANSFORMATIONS

PrPC

PrPSc

TRANSFORMATIONS

PrPC PrPSc

PROTEIN FOLDING BY CHAPERONS

Chaperon Proteins - provide a site where misfolded proteins can fold correctly

DIFFERENCE BETWEENPrPC and PrPSc

PrPC PrPSc

Solubility Soluble Non soluble

Structure Alpha-helix Beta-helix

Multimerisation Monomeric Multimeric

Infectivity Non infectious Infectious

Susceptibility to Proteinase K

Susceptible Resistant

INFECTIONo O – Origin of PRION

Contaminated meat

o Digestive Tracko Blood Streamo S – Spleeno N – Spleen to Brain o B – Brain

PATHOGENESIS

NEURODEGENERATIVE DISEASES CAUSED BY

PRIONSDisease Description

Infectious Diseases

Kuru • Human disease• Begins with a loss of coordination• followed by dementia

Scrapie • Disease of sheep and pigs• Characterized by intense itching in which animals

tend to scrape themselves into the trees• Followed by neurodegeneration

Mad cow disease (BSE) • Begins with changes in posture and temperament• Followed by loss of coordination and

neurodegeneration

Human Inherited Diseases

Creutzfeldt-Jakob disease • Characterized by loss of coordination and dementia

Gerstmann-Straussler-Scheinker disease

• Characterized by loss of coordination and dementia

Familial fatal insomnia • Begins w/ sleeping and ANS disturbances• Followed by insomnia and dementia

RESULT

BSESCRAPIE

RESULT

CONCLUSIONo Cook the meat thoroughly.

o If you are a raiser of cow, pig, sheep or a goat, check the list of the signs of prion diseases.

o If you think you have the early signs of the disease, immediately consult to a doctor.

References:1. McKintosh, E. et.al, 2003. Prion Diseases

2. Collinge, J., 2001. Prion Diseases of Humans and Animals: Their Causes and Molecular Basis

3. Belay, E.D., 1999. Transmissible Spongiform Encephalopathies in Humans

4. Belay, E.D. and Schonberger, L.B., 2005. The Public Health Impact of Prion Diseases

5. George-Hyslop P., McLaurin, J., and Westaway, D., 2006. Human Prion Diseases and Protein Misfolding Disorders

6. Veith, N.M., 2008. Cellular Trafficking of the Pathogenic Prion Protein PrPSc and Phenotypic Characterization of Deletion Mutants in the Hydrophobic Domain of the Normal Prion ProteinC

7. Marsh, D., 2002. Mad Cow Disease: The Risks to Humans

8. Weissmann, C. et.al, 2002. Molecular Biology of Prions

9. Mahmoud, M.K.H., 2009. Studies on Pathogenic Mechanisms of Prion Diseases and Evaluation of Prion Strains Properties

10. Aguzzi, A., et.al, 2007. Molecular Mechanisms of Prion Pathogenesis

Thank You!

HAPPY VALENTiNE’S

DAY