prions

scrapie

a fatal degenerative disease affecting the central nervous system of sheep and goats (domesticated animals)

what are symptoms of scrapie

nervousness/aggression
intense rubbing (scraping)
tremors
significant weight loss with no decrease in appetite
hyperesthesia (increased sensitivity to sensory stimuli)
locomotor incoordination that progresses to recumbency and death

what is Bovine Spongiform Encephalopathy (BSE)

"progressive neurological disorder of cattle" (DOMESTICATED ANIMALS)
BSE is commonly known as 'mad-cow disease '

what is known about symptoms of BSE

similar to scrapie

what is chronic wasting disease (CWD)

a "progressive neurodegenerative disorder"
"affects deer, elk, reindeer, mouse" (the WILD ANIMALS)
-DRASTIC WEIGHTLOSS-

what are symptoms of CWD

drastic weight loss (wasting)
stumbling
listlesness

what does brain tissue of cattle brain with BSE look like

empty white spaces w/ no cells
missing chunks of cells

wha does healthy brain tissue of cattle brain look like (no BSE)

lots of filled pink space and no white empty spots

what is the structure of the nervous system

central nervous system (cns) and peripheral nervous system (pns)

what does the CNS consist of

brain and spinal cord

what does PNS consist of

nerves and sensory organs

what kinds of cell compromise the nervous system (brain cell)

neurons

what kind of cell compromises the nervous system (general name for 6 types of cells)

neuroglia

what kinds of cell compromise the nervous system (6 types glial cells)

ependymal cells (cns)
oligondendrocytes **** (cns)
astrocytes (cns)
microglia (cns)
satelite cells (pns)
schwann cells **** (pns)

what is the function of glial cells

maintain optimal environment for neuronal signaling
-providing additional O2 & nutrients to neurons

what are the structural and functional relationships between PNS neurons and Schwann cells

axons of most PNS neurons are coated by a series of Schwann cells (called myelin sheath)
a myelinated axon can transmit info much more quickly than unmyelinated axon can

differences between oligodendrocytes of cns and the schwann cells of pns

schwann cells: 1 cell to 1 axon
oligondendrocytes: 1 cell to 3 axons

what are proteins made of

linear series of covalently linked amino acids

are all proteins in their final working form linear in structure

no

do all proteins have the same size/shape/charge

no
(ex: think of of how when insulin binds to a receptor size,shape,charge is different)

what is an alpha helix

a helical arrangement of a series of amino acids that is held together by HYDROGEN BONDS

what is a beta pleated sheet

an approximate flat structure that is made of parallel linear sequences of amino acids; it is held together by HYDROGEN BONDS

what happens when molecules bind to each other

they change each other's shapes
(ex: think of oxygen on hemoglobin, oxyhemoglobin, deoxyhemoglobin)

why care about a change in shape

a change in shape can mean a change in function

what is the major prion protein (PrP)

PrP is a protein that is normally present in healthy human tissue: often describes as cellular PrP (PrP^c) to signify the healthy type

in which tissues can PrP^c can normally be found

PrP^c is ubiquitously expressed BUT:
it is abundantly present in the cns and the pns, glial cells of the cns, and testes, eyes, placenta, uterus

what is one function of cellular PrP

promoting myelination of axons by signaling a receptor protein in Schwann cells
-this means that schwann cells will be able to provide support (O2 and nutrients) to the neuron
-Gpr 126 protein on the p.m. of the schwann cell waits for signal of the PrP^c that is on the extracellular face of p.m. of the axon

what is a prion

"proteinaceous infectious particle which is resistant to inactivation by most procedures that modify nucleic acids"
-they are molecule of protein that can be infectious and cause the production of more proteins (prions)

when were prions discovered as an infectious particle

1982

can the structure of PrP^c change

yes
PrP^c can change to PrP^sc
Prpc is normal protein in healthy human
Prpsc is abnormal protein in disease condition- PRION

how does prpc change to prpsc

prpsc prion binds to normal prpc
prpsc imposes a conformational change onto prpc
prpc is changed to prpsc

what is unique about prions

Prpc is water soluble. Prpsc is insoluble and cant be digested.
-Prpsc binds to Prpc
-Structure of Prpc is changed into Prpsc structure
-So: the Prpsc protein can cause the formation of Prpsc from the existing population of normal Prpc molecules

how can ingested protein survive inside the lumen of the digestive sys

as known: Prpc CANT survive digestion by cattle, while Prpsc CAN
-Prpsc can survive the highly acidic environment of the gastric lumen, and cannot bed degraded by gastric and intestinal proteases

how can Prpsc move between organisms and the environment

animals can get it from anything really. ex: prions can infect mothers milk and the baby gets infected, or animals can get it from animal feed if was made from animals that were infected

how can prions be transmitted in the wild

prions can survive in the environment and be ingested by other animals

what are the known human prion diseases (4)

CJD
GSS
Fatal Familial Insomnia
Kuru (cannabilism?)

what is CJD

"a degenerative brain disorder that leads to dementia and ultimately death.

what are symptoms of CJD

personality changes
memory loss
impaired thinking
blurred vision or blindness
insomnia
incoordination
difficulty speaking/ swallowing
EVENTUALLY LEADS TO: coma, organ failure

are there different kinds of CJD (3)

85%sporadic CJD- appears even tho they have no known risk factors
10-15% hereditary CJD- person inherits a mutation in PRNP
acquired CJD- diseases transmitted by exposure to brain/NS tissue (vCJD) Variant CJD can be acquired by eating meat from cattle that have BSE

what are risk factors for CJD

usually develop later in life , 60s
people with familial CJD carry a mutation in the PRNP gene
People could have had transplants of infected tissue; it is possible to contract vCJD from eating contaminated beef (BSE) the same prion that causes BSE can cause produce vCJD

what is the structure of the small intestine

something that leaves the lumen of the digestive sys and enters human tissue has to cross only one think layer of epithelial cells

what are peyers patches

large groups of leukocytes that are in the wall of the small intestine

are peyers patches inside the blood

no, they are outside of the blood

how does prpsc cross the epithelium of the small intestine

prpsc can be transcytosed by intestinal cells (M cells)

what are m cells

they are like the water samplers that check the contents of the small intestine, and they transcytose (transport) the prpsc from the lumen into other side
note: that the prpsc made it all the way to the intestine since it cant be digested and is in insoluble

what are some ways in which we think that prions can be transmitted among cells

exocytosis to endocytosis
membrane-membrane contact
tunneling nanotubes (TNTs)
microvesicles (that travel through TNTs)
exosomes
synpases

how do we think prpsc can get to the human CNS (steps)

1. prpsc is transcytosed by intestinal epithelial cells (M cells) from the intestinal lumen into a peyers patch
2. macrophages endocytose prpsc molecules and carry them via lymph ducts to lymph nodes
3. prpsc is passed onto dendritic cells where it transfroms prpc into prpsc
4. at some point prpsc appears on nearby neurons
5. prpsc can transform neuronal local prpc into prpsc

how do we think prpsc can get to the human CNS

once prpsc enters a neuron of the intestine, prpsc can transfrom prpc along one or more neuronal membranes of the CNS

what is one way prpsc can damage nerve tissue

prpsc CANNOT signal membranal proteins in glial cells, resulting in degeneration of the myelin sheath and loss of support (O2 and nutrients) for the neuron
-Prpsc most likely affect the oligodendrocytes of the CNS

how can CJD be detected (3)

electroencephalography (EEG)
cerebrospinal fluid based tests
magnetic resonance imaging (MRI)

what is the fatality rate for CJD

"invaribaly fatal neurodegenerative disease"

are there any treatments for CJD

no

how many people are known to have died from CJD

as the years went by the deaths increased, but you need to consider that the populations also grew greatly during those years

how many people are known to have died from vCJD

229?

where did vCJD first outbreak

UK