TY - JOUR
T1 - Heterotypic amyloid interactions
T2 - Clues to polymorphic bias and selective cellular vulnerability?
AU - Louros, Nikolaos
AU - Schymkowitz, Joost
AU - Rousseau, Frederic
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/2
Y1 - 2022/2
N2 - The number of atomic-resolution structures of disease-associated amyloids has greatly increased in recent years. These structures have confirmed not only the polymorphic nature of amyloids but also the association of specific polymorphs to particular proteinopathies. These observations are strengthening the view that amyloid polymorphism is a marker for specific pathological subtypes (e.g. in tauopathies or synucleinopathies). The nature of this association and how it relates to the selective cellular vulnerability of amyloid nucleation, propagation and toxicity are still unclear. Here, we provide an overview of the mechanistic insights provided by recent patient-derived amyloid structures. We discuss the framework organisation of amyloid polymorphism and how heterotypic amyloid interactions with the physiological environment could modify the solubility and assembly of amyloidogenic proteins. We conclude by hypothesising how such interactions could contribute to selective cellular vulnerability.
AB - The number of atomic-resolution structures of disease-associated amyloids has greatly increased in recent years. These structures have confirmed not only the polymorphic nature of amyloids but also the association of specific polymorphs to particular proteinopathies. These observations are strengthening the view that amyloid polymorphism is a marker for specific pathological subtypes (e.g. in tauopathies or synucleinopathies). The nature of this association and how it relates to the selective cellular vulnerability of amyloid nucleation, propagation and toxicity are still unclear. Here, we provide an overview of the mechanistic insights provided by recent patient-derived amyloid structures. We discuss the framework organisation of amyloid polymorphism and how heterotypic amyloid interactions with the physiological environment could modify the solubility and assembly of amyloidogenic proteins. We conclude by hypothesising how such interactions could contribute to selective cellular vulnerability.
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U2 - 10.1016/j.sbi.2021.11.007
DO - 10.1016/j.sbi.2021.11.007
M3 - Review article
C2 - 34942566
AN - SCOPUS:85121426435
SN - 0959-440X
VL - 72
SP - 176
EP - 186
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
ER -