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Creutzfeldt-Jakob Disease. Presentation by: Stephie Abraham. What is CJD??. It is a rare, degenerative, and fatal brain disorder. Alternative name: Transmissible Spongiform Encephalopathy Commonly affects people above 60. 90% of patients die within a year. 3 Types. Sporadic CJD - PowerPoint PPT Presentation
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Presentation by:
Stephie Abraham
What is CJD??What is CJD??
It is a rare, degenerative, and fatal It is a rare, degenerative, and fatal brain disorder.brain disorder.
Alternative name:Alternative name:– Transmissible Spongiform Transmissible Spongiform
EncephalopathyEncephalopathy Commonly affects people above 60.Commonly affects people above 60. 90% of patients die within a year.90% of patients die within a year.
3 Types3 Types
Sporadic CJDSporadic CJD– Most commonMost common– Appears in a person with no known risk Appears in a person with no known risk
factors.factors.– 1 case per million in the US1 case per million in the US– Mean age is 62Mean age is 62
Hereditary CJDHereditary CJD– Appears in people who has had a family Appears in people who has had a family
history of CJD.history of CJD.– About 5-10% in the USAbout 5-10% in the US
Acquired CJDAcquired CJD– Exposure to infectious brain tissueExposure to infectious brain tissue– Least commonLeast common– Less than 1%Less than 1%
SymptomsSymptoms
Early Stages:Early Stages:– Problems with muscular coordinationProblems with muscular coordination– Personality changesPersonality changes– Impaired memoryImpaired memory– Impaired visionImpaired vision– MyoclonusMyoclonus– blindnessblindness
Later Stages:Later Stages:– Loss of ability to speak and moveLoss of ability to speak and move– Enter a comaEnter a coma– DeathDeath
CausesCauses
First theory:First theory:– CJD was caused by a slow-acting virusCJD was caused by a slow-acting virus
Problems:Problems:– The disease causing agent did not have The disease causing agent did not have
any characteristics similar to virus or any characteristics similar to virus or bacteria.bacteria. No nucleic acidNo nucleic acid Long incubation period- up to 40 yearsLong incubation period- up to 40 years Indestructible Indestructible
Second theorySecond theory– Proposed by Stanley Proposed by Stanley
PrusinerPrusiner– Disease was caused by Disease was caused by
PrionsPrions– Conformational change Conformational change
from cellular PrP to from cellular PrP to scrapie PrPscrapie PrP
PrionsPrions
““Proteinaceous infectious particle that Proteinaceous infectious particle that lacks a nucleic acid”lacks a nucleic acid”
Naturally occurring proteins in Naturally occurring proteins in mammalsmammals– Made of 253 amino acidsMade of 253 amino acids– High concentrations in the brain tissueHigh concentrations in the brain tissue– Initially encoded in chromosome 20 as Initially encoded in chromosome 20 as
amino acid residuesamino acid residues– Soluble in detergentsSoluble in detergents– Susceptible to enzyme digestionSusceptible to enzyme digestion
Rich in alpha-helical structure
N-terminal contains an octapeptide region
Disulfide linkage
PrP forms in PrP forms in the nucleus the nucleus
Translation of Translation of the ORFthe ORF
Endoplasmic Reticulum
Golgi Apparatus
Nucleus
Vesicles
Plasma Membrane
Post-translational Post-translational modificationsmodifications
Removal of the N-terminal 23 residue Removal of the N-terminal 23 residue signal peptidesignal peptide
Glycosylation at Asparagines 181 &197Glycosylation at Asparagines 181 &197 Formation of the disulfide bond Formation of the disulfide bond
between cysteine residues 179 & 214between cysteine residues 179 & 214 Proteolytic cleavage of the C-terminal Proteolytic cleavage of the C-terminal
24 amino acids24 amino acids Addition of Glycosyl Addition of Glycosyl
Phosphatidylinositol (GPI) anchorPhosphatidylinositol (GPI) anchor
Functions:Functions:– Cell adhesionCell adhesion– Signaling Signaling
processesprocesses– Copper transport Copper transport
or metabolismor metabolism
Scrapie PrP
Characteristics
• 43% beta sheet
• 30% alpha-helix
• Resistant to proteolytic digestion
• Insoluble in detergents
Scrapie PrP forces normal cellular PrP Scrapie PrP forces normal cellular PrP to change its form.to change its form.
Aggregates are formed Aggregates are formed Cell death occursCell death occurs
TreatmentTreatment– No known cureNo known cure
Current ResearchCurrent Research– Focused on the mechanism of Focused on the mechanism of
transformation of normal PrP to scrapie transformation of normal PrP to scrapie PrP. PrP.
Questions???Questions???
The End The End !!!!!!