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Unformatted text preview: 2004 Jul;10 Suppl:S10-7. Review. protein Misfolding -AB
deposit within brain ND
disorders/ hydrophobic/ How proteins aggregate and form insoluble
fibrils Whats toxic?
if protein isn’t in its state /
thats when it becomes
toxic , when it makes
deposit in brain ( less
toxic). Protein oxidation…
Can cause proteins to
agregate Representation of structural components of
protein structure Protein folding and energy states protein happiesst wen they are
folded. native proteins are
avtive/ protein misfolding
happes a lot trought its life time,
increase intracellular Ph ,
protein can fold back to its
original form • Protein folding: Only folded, native proteins are functionally active • Unfolded states: Characterized by higher degree of free energy than native states. This leads to “unstableness” of proteins when
in the unfolded state. The minimum of the energy level of a
protein is reached when it’s in its native/folded state. • Protein misfolding: A common and continuous phenomenon in the life of a protein • Denaturation: The process by which the native structure of protein is disrupted Protein Aggregation
• If a protein is damaged it can undergo denaturation, this causes loss of the low energy state.
because its high energy wants to go to low
energy its forms aggregate state • The protein is then in a highly disorganized structure and tends to form aggregates to reduce the state of high energy.
i.e. to stabilize Summary of protein misfolding diseases Factors that might influence protein
denaturation and misfolding
• Mutations protein are in monomers , one AA
chain ,lot more chance to form
aggregate then if you only have
one AA around • Glucose levels
• Changes in physiological pH
• Binding to ions
• Levels/concentrations of monomers: if low the protein tends not to aggregate, if high the protein tends to form aggregates Schematic representation of protein
Something will cause it to
unfold, it can form ﬁbrils,
photo ﬁbrils then amyloid
plaques, all intermediates
are toxic to
cell.intermediates are more
toxic then AP themselves • Pathways to...
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This document was uploaded on 02/03/2014.
- Winter '14