当前位置： SCI文献检索 > BIOCHEMISTRY期刊下所有文献 > Conformational Dynamics of Specific Aβ Oligomers Govern Their Ability To Replicate and Induce Neuronal Apoptosis.

Conformational Dynamics of Specific Aβ Oligomers Govern Their Ability To Replicate and Induce Neuronal Apoptosis.

Abstract：

:Oligomers of amyloid-β (Aβ) have emerged as the primary toxic agents responsible for early synaptic dysfunction and neuronal death in Alzheimer's disease (AD). Characterization of oligomers is an important step in the progress toward delineating the complex molecular mechanisms involved in AD pathogenesis. In our previous reports, we established that a distinct 12-24mer neurotoxic oligomer of Aβ42, called Large Fatty Acid derived Oligomers (LFAOs), exhibits a unique property of replication in which LFAOs directly duplicate to quantitatively larger amounts upon interacting with monomers. This self-propagative process of replication is somewhat reminiscent of prion propagation. In this report, we sought to investigate the concentration-dependent conformational dynamics LFAOs undergo and how such transitions manifest in their ability to replicate and induce neuronal apoptosis. The results indicate that LFAOs undergo a concentration-dependent transition between 12mers and disperse 12-24mers with a dissociation constant (Kd) of 0.1 μM. The two species differ in their respective tertiary/quaternary structures but not their secondary structures. This conformational dynamics of LFAOs correlates with their ability to replicate and to induce apoptosis in SH-SY5Y human neuroblastoma cells, with 12mers being more neurotoxic and prone to replication than 12-24mers. The latter result implicates the replication process dominates at low physiological concentrations. The observations made in this report may have profound significance in deciphering the elusive roles of Aβ oligomer phenotypes and in determining their prion-type behavior in AD pathology.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Dean DN,Pate KM,Moss MA,Rangachari V

doi

10.1021/acs.biochem.6b00161

subject

Has Abstract

pub_date

2016-04-19 00:00:00

pages

2238-50

issue

15

eissn

0006-2960

issn

1520-4995

journal_volume

55

pub_type

杂志文章

相关文献

BIOCHEMISTRY文献大全