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SICK CHAPERONES, CELLULAR
STRESS, AND DISEASE
Meutia Atika Faradilla
Postgraduate biomedical scienceFaculty of medicine
University sumatera utara2016
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Stressor Type
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Cellular stress and protein damaged
stressorinhibit house
keeping genedan increase
stress gen
Increaseprotein stress
Proteindenaturation
Failure ofprotein
folding andbecomeinclusionbodies
Cellulardamage andpathological
things happen
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Protein folding diagram
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Heat shock protein dan chaperon
Heat shockprotein
A group of protein
produced by cell due toexposure to stress condition
(heat shock)
chaperonA Group of protein that helpfold and unfold
macromollecular structure
Only a fraction of chaperones are encoded in genesthat are inducible by stressors and thus belong to the
large class of stress proteins.If the stressor is heat shock, the induced chaperones are
named heat-shock proteins (HSPs).Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Heat shock protein and chaperon
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Heat shock protein function
HSP refold unfolding protein from reticullum endoplasmic
Help eliminate irreversible damage protein
Innate imunostimulator
Decrease proinfalamation cytokine
Protect cells from stressor
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Function of chaperon
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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chaperonopathies
Mutation on chaperon gene causedefunction chaperon (genetic defect)
Failure of chaperon during post translationmodification ( acquired defect)
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Genetic chaperonopathies
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Acquired Chaperonopathies associated withaging and disease
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Aqcuired Chaperonopathies associatedwith aging and disease
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Crystallins on neurodegenerative disease,myositis, catarac and retinophaty
• Abnormality of crystallindistribution associated withdiseases :
• Alzheimer, glial inclussion oftaupathies
Neurodegenerativedisease
• reduction crystallin function
cause lens opacitycatarac
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Crystallins on neurodegenerative disease,myositis, catarac and retinophaty
• Reduction crystallinfunction as chaperon
• Increase age related
retinophaty
Retinophati
• Myositis happen fasterin 50 years old.Myositis
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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Another condition associated withchaperon
Von hippel-lindau disease• mutation on von hipple-lindau segmen
• Failure of chaperon machine to recognizechaperon recognition site
Autoantibodies attack chaperon• Change of chaperon structure because of
mutation or post translation modificationcause chaperon become autoantigen andtrigger autoimmune respone
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
P li fi f h
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Polimorfisme of chaperon gene
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501
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