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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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