Biotech Project FINAL Final

8/3/2019 Biotech Project FINAL Final

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DISCOVERY OFPRIONS


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PrPchas neuro protective properties


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Properties PrPc PrPsc

Isoform Normal Pathogenic

Protease resistance NoStable core containing

residue 90-231Location in or on cells Plasma membrane Cytoplasmic vesicles

Solubility Soluble Insoluble

PKsensitivity Sensitive Partially resistant

Structure Extended Globular

Helices 45% 30%

Sheets 3% 45%

Glycoforms

Mixture of un, mono

and diglycosylatedforms

Mixture of un, mono

and diglycosylatedforms

Infectivity No Yes

Turnover Hours Days

Sedimentation Consistent with Multimeric aggregated


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Aggregations of the abnormal prionsform highly structured amyloid

fibers, which accumulate to formplaques.


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Prions cause neurodegenerative disease byaggregating extracellular within thecentral nervous system to form plaquesknown as amyloids, which disrupt the

normal tissue structure. This disruption ischaracterized by "holes" in the tissue withresultant spongy architecture due to thevacuole formation in the neurons. Otherchanges include astrogliosis and theabsence of an inflammatory reaction.


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The Route of Prion Neuro

invasion


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Examples of Prion Diseases-Kuru in humansCreutzfeldt-Jakob Disease in humansScrapie in sheeps and goatsMad cow disease. Etc


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Ewe with scrapie with weight lossand hunched appearance

Same ewe with bare patches on rearend from scraping


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Common Symptoms of Prion Diseases inhumans-1 Rapidly developing delirium ordementia (over the course of a fewweeks or months)2 Blurred vision (sometimes)

3 Changes in gait (walking)4 Hallucinations5 Lack of coordination (for example,stumbling and falling)

6 Muscle twitching7 Muscle stiffness8 Myoclonic jerks or seizures9 Nervous, jumpy feelings


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10 Personality changes11 Profound confusion, disorientation12 Sleepiness13 Speech impairment

1 Change in attitude and behaviour2 Uncoordinated movements3 Trouble standing and walking4 Weight loss5 Excessive lip-smacking


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The incubation period for prion diseases isgenerally quite long, once symptoms

appear the disease progresses rapidly,leading to brain damage and death.

Currently available tests for priondiseases identify the abnormally-foldedprion protein in brains of infected or deadanimals through either antibody- orWestern blot-based technologies. To date,no tests can identify the presence of thedisease-causing proteins in easily

accessible blood or tissues.


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Disease can be confirmed only upon theappearance of outward symptoms and/or

the availability of post-mortem brain andnervous symptom tissues which areexamined immunohistochemically.

A test is now available to detect scrapiewhich is performed by sampling a smallamount of lymphatic tissue from the thirdeyelid.


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Prion diseases are invariably fatal and notreatments are yet available.other medications may be use in an

attempt to slow the progression of thedisease.Custodial care may be required early inthe course of the disease. Medications may

be needed to control aggressive behaviours.


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There are probably at least three reasons-

The one that's most often put forward is thatprion proteins are normal self proteins

prion proteins tend to be intracellular. Antibodies,which are the best components of the immunesystem for recognizing folding configurations, aremost responsive to extracellular proteins, and the

components of the immune system that are focusedon intracellular targets are less sensitive to folding.

lack of innate immune stimulation, that is,inflammation


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Biotech Project FINAL Final

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