SICK CHAPERONES, CELLULAR

STRESS, AND DISEASE

Meutia Atika Faradilla

Postgraduate biomedical science

Faculty of medicine
University sumatera utara
2016

Stressor Type

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Cellular stress and protein damaged

stressor

Cellular
damage and
pathological
things happen

inhibit house
keeping gene
dan increase
stress gen
Failure of
protein
folding and
become
inclusion
bodies

Increase
protein stress

Protein
denaturation

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Protein folding diagram

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Heat shock protein dan chaperon

Heat shock
protein

A group of protein
produced by cell due to
exposure to stress condition
(heat shock)

chaperon

A Group of protein that help

fold and unfold
macromollecular structure

Only a fraction of chaperones are encoded in genes

that 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

Heat shock protein and chaperon

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

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

Function of chaperon

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

chaperonopathies
Mutation on chaperon gene cause
defunction chaperon (genetic defect)

Failure of chaperon during post translation

modification ( acquired defect)

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Genetic chaperonopathies

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Acquired Chaperonopathies associated with

aging and disease

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Aqcuired Chaperonopathies associated

with aging and disease

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Crystallins on neurodegenerative disease,

myositis, catarac and retinophaty
Abnormality of crystallin
distribution associated with
Neurodegenerative diseases :
disease
Alzheimer, glial inclussion of
taupathies

catarac

reduction crystallin function

cause lens opacity

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Crystallins on neurodegenerative disease,

myositis, catarac and retinophaty

Retinophati

Myositis

Reduction crystallin
function as chaperon
Increase age related
retinophaty

Myositis happen faster

in 50 years old.

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Another condition associated with

chaperon

Von hippel-lindau disease

mutation on von hipple-lindau segmen
Failure of chaperon machine to recognize
chaperon recognition site

Autoantibodies attack chaperon

Change of chaperon structure because of
mutation or post translation modification
cause chaperon become autoantigen and
trigger autoimmune respone
Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501

Polimorfisme of chaperon gene

Alberto and Everli. 2005. Sick chaperones, cellular stress nd disease. NEJM. 353:1489-501