Skip to main content
placeholder image

The role of amyloid oligomers in neurodegenerative pathologies

Journal Article


Abstract


  • Many neurodegenerative diseases are rooted in the activities of amyloid-like proteins which possess conformations that spread to healthy proteins. These include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). While their clinical manifestations vary, their protein-level mechanisms are remarkably similar. Aberrant monomeric proteins undergo conformational shifts, facilitating aggregation and formation of solid fibrils. However, there is growing evidence that intermediate oligomeric stages are key drivers of neuronal toxicity. Analysis of protein dynamics is complicated by the fact that nucleation and growth of amyloid-like proteins is not a linear pathway. Feedback within this pathway results in exponential acceleration of aggregation, but activities exerted by oligomers and fibrils can alter cellular interactions and the cellular environment as a whole. The resulting cascade of effects likely contributes to the late onset and accelerating progression of amyloid-like protein disorders and the widespread effects they have on the body. In this review we explore the amyloid-like proteins associated with AD, PD, HD and ALS, as well as the common mechanisms of amyloid-like protein nucleation and aggregation. From this, we identify core elements of pathological progression which have been targeted for therapies, and which may become future therapeutic targets.

Publication Date


  • 2021

Citation


  • Wells, C., Brennan, S., Keon, M., & Ooi, L. (2021). The role of amyloid oligomers in neurodegenerative pathologies. International Journal of Biological Macromolecules, 181, 582-604. doi:10.1016/j.ijbiomac.2021.03.113

Scopus Eid


  • 2-s2.0-85103707511

Start Page


  • 582

End Page


  • 604

Volume


  • 181

Issue


Place Of Publication


Abstract


  • Many neurodegenerative diseases are rooted in the activities of amyloid-like proteins which possess conformations that spread to healthy proteins. These include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). While their clinical manifestations vary, their protein-level mechanisms are remarkably similar. Aberrant monomeric proteins undergo conformational shifts, facilitating aggregation and formation of solid fibrils. However, there is growing evidence that intermediate oligomeric stages are key drivers of neuronal toxicity. Analysis of protein dynamics is complicated by the fact that nucleation and growth of amyloid-like proteins is not a linear pathway. Feedback within this pathway results in exponential acceleration of aggregation, but activities exerted by oligomers and fibrils can alter cellular interactions and the cellular environment as a whole. The resulting cascade of effects likely contributes to the late onset and accelerating progression of amyloid-like protein disorders and the widespread effects they have on the body. In this review we explore the amyloid-like proteins associated with AD, PD, HD and ALS, as well as the common mechanisms of amyloid-like protein nucleation and aggregation. From this, we identify core elements of pathological progression which have been targeted for therapies, and which may become future therapeutic targets.

Publication Date


  • 2021

Citation


  • Wells, C., Brennan, S., Keon, M., & Ooi, L. (2021). The role of amyloid oligomers in neurodegenerative pathologies. International Journal of Biological Macromolecules, 181, 582-604. doi:10.1016/j.ijbiomac.2021.03.113

Scopus Eid


  • 2-s2.0-85103707511

Start Page


  • 582

End Page


  • 604

Volume


  • 181

Issue


Place Of Publication