Toggle Main Menu Toggle Search

Open Access padlockePrints

The effects of the novel A53E alpha-synuclein mutation on its oligomerization and aggregation

Lookup NU author(s): Professor Tiago Outeiro

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

α-synuclein (aSyn) is associated with both sporadic and familial forms of Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease. In particular, multiplications and point mutations in the gene encoding for aSyn cause familial forms of PD. Moreover, the accumulation of aSyn in Lewy Bodies and Lewy neurites in disorders such as PD, dementia with Lewy bodies, or multiple system atrophy, suggests aSyn misfolding and aggregation plays an important role in these disorders, collectively known as synucleinopathies. The exact function of aSyn remains unclear, but it is known to be associated with vesicles and membranes, and to have an impact on important cellular functions such as intracellular trafficking and protein degradation systems, leading to cellular pathologies that can be readily studied in cell-based models. Thus, understanding the molecular effects of aSyn point mutations may provide important insight into the molecular mechanisms underlying disease onset.We investigated the effect of the recently identified A53E aSyn mutation. Combining in vitro studies with studies in cell models, we found that this mutation reduces aSyn aggregation and increases proteasome activity, altering normal proteostasis.We observed that, in our experimental paradigms, the A53E mutation affects specific steps of the aggregation process of aSyn and different cellular processes, providing novel ideas about the molecular mechanisms involved in synucleinopathies.


Publication metadata

Author(s): Lazaro DF, Dias MC, Carija A, Navarro S, Madaleno CS, Tenreiro S, Ventura S, Outeiro TF

Publication type: Article

Publication status: Published

Journal: Acta neuropathologica communications

Year: 2016

Volume: 4

Online publication date: 09/12/2016

Acceptance date: 03/12/2016

Date deposited: 19/12/2017

ISSN (electronic): 2051-5960

Publisher: BioMed Central Ltd.

URL: https://doi.org/10.1186/s40478-016-0402-8

DOI: 10.1186/s40478-016-0402-8

PubMed id: 27938414


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share