By : Amirah nu’aimi Sharifah Nurul Hanim

TASK 2 – DISCUSS THE EXAMPLE OF PROTEIN FOLDING DISEASE BY STATING

THE MECHANISM

Misfolded protein causes : • prion-related illnesses - bovine spongiform

encephalopathy (mad cow disease),• amyloid-related illnesses - Alzheimer‘

disease• intracytoplasmic aggregation diseases -

Parkinson's disease.

PRION

• Prion (protenaceous infectious particles) diseases are self-propagating and transmissible

• There act as infectious agent.• prion contain no nucleic acid, and their chemistry

and structure are not like those of bacteria or viruses.

• Resistance to heat, radiating, proteolytic enzyme, and conventional disenfactant

Normal prion (PrP C) - 42% a-helix, 3% b-sheetDiseased prion (PrP Sc) - 43% a-helix, 30% b-sheet

MECHANISM1. Protein that prion made

of known as (PrP). PrPC is a normal protien found on the membranes of cells (mainly a- helical structure)

2. PrPC through breakage, nucleation or infection will transform into PrPSc, ( sc stand for scarpie ). has a higher proportion of β-sheet structure in place of the normal α-helix structure

3. PrPSc, is able to convert normal PrPC proteins into the infectious isoform by changing their conformation, or shape..

4. Aggregations of these abnormal isoforms form highly structured amyloid fibers, which accumulate to form plaques

6. The PrPSc molecules then come apart and can go on to convert more PrPC

5. The end of each fiber acts as a template onto which free protein molecules may attach, allowing the fiber to grow.

Accumulation of prp (sc)

Bovine Spongiform Encephalopathy

• Commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord.

• Usually affecting adult cattle at a peak age onset of four to five years, all breeds being equally susceptible.

Transmission

• The disease may be most easily transmitted to human beings by eating food contaminated with the brain, spinal cord or digestive tract of infected carcasses.

• However, it should also be noted that the infectious agent, although most highly concentrated in nervous tissue, can be found in virtually all tissues throughout the body, including blood.

• In humans, it is known as new variant Creutzfeldt–Jakob disease.

Symptoms

• The first symptoms of BSE are typically an odd change in activity and attitude of the cattle.

• Then the infected animal will begin to become increasingly uncoordinated and have trouble performing simple movements, such as walking and standing.

• The cow may then experience a noticeable decrease in weight, without any loss of appetite and it may begin to lag in milk production.

• These symptoms may become worse and worse, until the animal eventually dies.

Creutzfeldt–Jakob Disease

• Creutzfeldt–Jakob disease (CJD) is a degenerative neurological disorder (brain disease) that is incurable and invariably fatal.

• CJD is at times called a human form of mad cow disease, given that bovine spongiform encephalopathy is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.

• In CJD, the brain tissue develops holes and takes on a sponge-like texture. This is due to a type of infectious protein called a prion.

• Prions are misfolded proteins which replicate by converting their properly folded counterparts.

Symptoms

• The symptoms of BSE in humans are similar to those in cattle.

• People who have variant Creutzfeldt-Jacob Disease (vCJD) usually begin to lose their ability to remember, concentrate, and judge things and situations.

• As the disease progresses, some patients have strong difficulties with movement and experience severe muscle jerks.

• These serious symptoms continue until the infected patient falls tragically into a coma and eventually dies.

reference

• Protein folding - Wikipedia, the free encyclopedia.mht

• Prion - Wikipedia, the free encyclopedia.mht• Prion diseases.htm