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What drives an amyloid protein precursor from an amyloidogenic to a native-like aggregation pathway?
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Authors
Advisor(s)
Abstract(s)
Conformational disorders such as
Alzheimer’s, Parkinson’s, familial
amyloidotic polyneuropathy and
spongiform encephalopaties are
a consequence of protein misfolding
and aggregation predominantly
in the form of amyloid fibrils. These
pathologies represent a major health
problem, which most probably will
overwhelm the health systems of
developed countries in the near
future. Significant progress has been
made recently to understanding the
underlying mechanism of protein
misfolding and aggregation. The current
picture of protein aggregation is
a phenomenon resulting from protein
conformational fluctuations leading
to misfolded intermediates prone to
form non-native interactions with
other intermediates, resulting in
amyloid fibril formation. Fortunately
just a small group of proteins are
associated with human conformational
disorders. The primary causes
that lead this group of proteins to
misfolding and aggregation are point
mutations, protein over-expression
and failure of protein quality-control
system. Beside amyloid formation,
there are other types of aggregation
available to a misfold-disease-related
polypeptide chain in the proteinfree
energy landscape. Among them,
native-like aggregation is becoming a
widely studied topic of research.
This aggregation type, simultaneously straightforward and ubiquitous, seems to be involved concurrently in the pathway of amyloid fibril formation and disruption. In this review, the pathways of misfold and aggregation of a protein are accessed along with the primary causes that turn a native soluble protein into amyloid fibrils or native-like aggregate. In addition, an insight into the biophysical and biochemical aspects fundamental to amyloid fibril formation and nativelike aggregation is provided. Finally some clues are presented about what makes a protein follow an amyloidogenic or native-like aggregation pathway.
Conclusion: More laboratory data should be gathered about the structure, stability, dynamics and aggregation kinetics, in order to get a clearer picture of the biophysical mechanisms underlying native-like aggregation.
This aggregation type, simultaneously straightforward and ubiquitous, seems to be involved concurrently in the pathway of amyloid fibril formation and disruption. In this review, the pathways of misfold and aggregation of a protein are accessed along with the primary causes that turn a native soluble protein into amyloid fibrils or native-like aggregate. In addition, an insight into the biophysical and biochemical aspects fundamental to amyloid fibril formation and nativelike aggregation is provided. Finally some clues are presented about what makes a protein follow an amyloidogenic or native-like aggregation pathway.
Conclusion: More laboratory data should be gathered about the structure, stability, dynamics and aggregation kinetics, in order to get a clearer picture of the biophysical mechanisms underlying native-like aggregation.
Description
Keywords
protein misfolding protein aggregation amyloid fibrils human conformational disorders native-like aggregation
Citation
Quintas A. What drives an amyloid protein precursor from an amyloidogenic to a native-like aggregation pathway? OA Biochemistry 2013 Mar 01;1(1):6.