L13 Prions Disease

Question 1

What is Prions Disease

Answer 1

A neurodegenerative disease characterised by the accumulation of a misfolded isoform of prion protein in the CNS and the Periphery

Question 2

Discuss prions protein normal and abnormal

Answer 2

Prions can exist normally as an innocuous cellular protein

BUT it has the ability to fold into highly stable conformations resulting in harmful particles

Causes brain disease

Question 3

Show the protein properties of normal and abnormal prion protein

Answer 3

Prp= PrPSc (DISEASE)

PrP= PrPc (Normal)

Question 4

Protein Folding

Answer 4

Primary - sequence of a chain of amino acids

Secondary- hydrogen bonding of the peptide causes the amino acids to fold into a repeating pattern

Tertiary- three dimensional folding pattern of a protein due to side chain interactions

Quaternary- protein consisting of more than one amino acid chain

Question 5

Normal vs Abnormal protein

Answer 5

Although PrPc and PrPsc do not differ in sequence of amino acids. The conformation change from normal to abnormal induces the formation of neurotoxic amyloid aggregates

Question 6

Characteristics of Prions Disease

Answer 6

No antibiotic can cure it

Not typical eukaryotic or prokaryotic organism

Resistant to digestion

Resistent to high temp and disinfectants

Non immunogens and dont trigger an immune response

Not easy to decompose biologically

Question 7

Neuropathology of a brain that is diseased

Answer 7

Diseased brain have a characteristic porous and spongy appearance

Question 8

What do affected individuals of Prions disease exhibit

Answer 8

Rapidly developing dementia
Difficulty walking
Hallucinations
Muscle stiffness
Confusion
Fatigue
Difficulty speaking

Question 9

Infective Process of Prions Disease

Answer 9

Blood transfusion, hormonal supplements

Eating contaminated meat

Transplantation with affected organs

Inherited

Spontaneuos mutations

Question 10

Kuru Disease

Answer 10

Caused through ritualistic cannabilistic practice

Pathology
-Prodormal-headache and limb/joint pain

-Ambulant - unable to walk without a stick

-Sedentary- unable to walk without support

Terminal-bed ridden

Question 11

Creutzfeld Jacob Disease (CDJ)

Answer 11

Can be sporadic, variant and familial

Fatal degeneration of brain tissue and nervous system

Loss of expressiveness
Muscular tremble
Spasm
Impaired muscle coordination
Loss of memory and dementia

Question 12

VCDJ - Mad Cow Disease

Answer 12

Consumption of tainted meat

Clusters of amyloid plaques across the cerebellum and basal ganglia

Psychiatric symptoms

Question 13

Gertsman- Straussler Scheinker Syndrome (GSS)

Answer 13

Inherited disorder (autosomal dominant)

Very rare

Onset is between 40-70, lasts approx 5 years

Progressive ataxia, dementia, encephalopathy and multicentric PrP plaque build up

Question 14

Familial Fatal Insomnia

Answer 14

Inherited Disorder

FFI is a rare genetic degenerative brain disorder.

Characterized by inability to sleep, starts mild and progresses to become mentally and physically detiorating

Caused by abnormal variant in the prion protein gene but can also occur sporadically

Question 15

Therapy

Answer 15

Incurable and Untreatable

Research:
- Stem cell therapy
-Gene Silencing
-Antibodies against PrP
-Small molecule drugs

Question 15

Management

Answer 15

Palliative Care
Organ Donation
Nasogastric Tube
Mechanical Ventilation