Papadopoulos, N.; Suelves, N.; Perrin, F.; Vadukul, D.M.; Vrancx, C.; Constantinescu, S.N.; Kienlen-Campard, P. Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates. Biomedicines2022, 10, 2753.
Papadopoulos, N.; Suelves, N.; Perrin, F.; Vadukul, D.M.; Vrancx, C.; Constantinescu, S.N.; Kienlen-Campard, P. Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates. Biomedicines 2022, 10, 2753.
Papadopoulos, N.; Suelves, N.; Perrin, F.; Vadukul, D.M.; Vrancx, C.; Constantinescu, S.N.; Kienlen-Campard, P. Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates. Biomedicines2022, 10, 2753.
Papadopoulos, N.; Suelves, N.; Perrin, F.; Vadukul, D.M.; Vrancx, C.; Constantinescu, S.N.; Kienlen-Campard, P. Structural Determinant of β-Amyloid Formation: From Transmembrane Protein Dimerization to β-Amyloid Aggregates. Biomedicines 2022, 10, 2753.
Abstract
Most neurodegenerative diseases have the characteristics of proteinopathies, i.e. they cause lesions to appear in vulnerable regions of the nervous system, corresponding to protein aggregates that progressively spread through the neuronal network as the symptoms progress. Alzheimer's disease is one of these proteinopathies. It is characterized by two lesions, neurofibrillary tangles (NFTs) and senile plaques, formed essentially of amyloid peptides (Aβ). A combination of factors ranging from genetic mutations to age-related changes in the cellular context converge in this disease to accelerate Aβ deposition. Over the last two decades, numerous studies have attempted to elucidate how structural determinants of its precursor (APP) modify Aβ production, and to understand the processes leading to the formation of different Aβ aggregates; e.g. fibrils and oligomers. The synthesis proposed in this review indicates that the same motifs can control APP function and Aβ production essentially by regulating membrane dimerization, and subsequently Aβ aggregation processes. The distinct properties of these motifs and the cellular context regulate the APP conformation to trigger the transition to the amyloid pathology. This concept can be transposed to the study of other proteinopathies, providing a framework for improving our understanding of these mechanisms that devastate neuronal functions.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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