Biology 103 - Microbes and You

Lecture 16 Outline

Mad Cow Disease (prions)


Kuru region of Papua/New Guinea

Brain tissue with spongiform encephalopathy

Amyloid plaques in brain tissue

More amyloid plaques in the brain

Relative risk of dying from CJD

UV effects on infectious agents

Protein ribbon diagram showing normal and rogue prion conformaitons

Animation of conformational change from normal to rogue prion

Protein beta-sheet conformation

Fiber of rogue prions

Four fibers of rogue prions

Structural comparison of mouse and hamster prions

Mad cow joke

Prions start with D. Carlton Gajdusek
he studied a disease called "laughing death" in tribes in the Kuru region of Papua/New Guinea in the late 1950's
the disease causes symptoms that include dementia (hence the laughing) and lead to death
the brains of infected individuals exhibited a pattern known as spongiform encephalopathy
here, brain tissue is lost through the death of neurons, leaving open areas and a brain that looks like a sponge
the death of brain tissue leads to dementia and eventually more serious neurological problems
neurons are long cells that look like dumbbells - cell bodies on the ends of a long shaft
there are fibers that run the length of these long shafts
when the neuron dies, the fibers are released and form neurofibrillar tangles
eventually these tangles become calcified and form plaques that are readily observable

the symptoms of Kuru disease are similar to other dementias
these dementias are "presenile", occurring before age 65
the pathology and progress of the disease is similar to what we call Alzheimer's disease
the symptoms are also like senility, a less acceptable term today
the difference between Kuru disease and senility is that Kuru is transmissible
in the Kuru tribes, cannibalism and eating the brains of respected tribe members after death was common
this is how the Kuru infective agent was transmitted

first guess would be that Kuru was caused by a virus
but no virus was found
the infectious agent was very small, like a virus
but it contained no detectable nucleic acid
and UV light that mutates DNA (and kills viruses and bacteria) does not affect the infectious agent of Kuru
it is believed to be a protein
the term prion was coined to describe these "proteinaceous infectious particles"

Prions are a form of protein already present in healthy brains, although its role is unknown
in Kuru the prion protein is changed into a different form, the "rogue" protein
the change that occurs is in the folding of the polypeptide chain
remember that proteins are polymers (linear chains) of amino acids
the protein chain has a backbone and side chains that hang off of the backbone
the protein chain folds up and has a defined 3-dimensional structure
we can draw this structure using a ribbon diagram that shows the backbone of the polypeptide
there are various folding patterns that we have identified: alpha helices, beta sheets, random coils
the healthy prion has lots of alpha helices
the rogue prion has lots of beta sheets
they are the same protein, just folded differently
current theories say that the rogue protein helps convert other healthy prions into the rogue conformation
the rogue proteins eventually assemble into large structures and fibers
these fibers collect in the brain causing plaque formation and death of neurons and dementia

Other diseases caused by prions
Mad cow disease - BSE - Bovine spongiform encephalopathy
Scrapie in sheep - they scrape off their fur
Can we catch these diseases? Yes.
Close contact with infected sheep or cows or eating their flesh may transmit the prion disease
it is hard to get a away from animal products - even gelatin capsules and cosmetics contain materials from rendering (boiling up) the carcasses of animals

Other human prion diseases
CJD - Creutzfeldt-Jakob Disease - affects 1 million people annually worldwide, usually after age 60
CJD can be contracted by genetic inheritance, sporadically (randomly), and through infection from sheep or humans (organ transplantation)
GSS - Gertsmann-Straussler-Scheinker - an inherited dementia
Fatal familial insomnia - an inherited dementia that attacks in mid-life
the inherited forms of the prion diseases occur because of mutations in the prion genes
hence, the mutated prion gene in the persons brain makes a prion that tends to fold into the rogue conformation often enough to lead to disease
these mutations can be passed from generation to generation

Discussion about the J. Bacteriology article.

Description of gel electrophoresis
gel electrophoresis is used to separate proteins, DNA or RNA
a slab of agarose gelatin is poured
little slots or wells are added and a DNA solution is added
the gel is submerged in a salt solution and electricity is applied across the gel
since DNA is negatively charged, it moves towards the positive pole
as it moves, it snakes its way through the maze of the gel material
smaller objects can move through the pores more easily and travel faster in the gel
larger objects move slower during electrophoresis
thus small DNA molecules end up at the bottom of the gel closest to the positive pole
and large DNAs are closer to the wells, having not moved very far
in this way DNA molecules can be separated based on their size (number of base pairs)
RNA can be separated in the same way
proteins can be separated too
generally proteins are separated on very thin gels of polyacrylamide poured between two glass plates
electrophoresis is then performed and proteins (which are generally negatively charged) move toward the positive pole
again larger proteins move slower than smaller proteins
in this way proteins can be separated by size
individual protein or DNA bands can be cut from gels and purified for further study

Back to BIOL 103 Homepage