Imperial College London
Portrait Picture

DrJavierAlegre Abarrategui

Faculty of Medicine, Department of Brain Sciences

Clinical Senior Lecturer in Neuropathology
 
 
 
//

Contact

 

+44 (0)20 7594 6683j.alegre

 
 
//

Assistant

 

Mrs Hadeel Abdeen +44 (0)20 7594 7014

 
//

Location

 

E416Burlington DanesHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Hunn:2019:10.1016/j.celrep.2019.09.029,
author = {Hunn, BHM and Vingill, S and Threlfell, S and Alegre-Abarrategui, J and Magdelyns, M and Deltheil, T and Bengoa-Vergniory, N and Oliver, PL and Cioroch, M and Doig, NM and Bannerman, DM and Cragg, SJ and Wade-Martins, R},
doi = {10.1016/j.celrep.2019.09.029},
journal = {Cell Reports},
pages = {920--e7},
title = {Impairment of macroautophagy in dopamine neurons has opposing effects on Parkinsonian pathology and behavior},
url = {http://dx.doi.org/10.1016/j.celrep.2019.09.029},
volume = {29},
year = {2019}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Parkinson’s disease (PD) is characterized by the death of dopamine neurons in the substantia nigra pars compacta (SNc) and accumulation of α-synuclein. Impaired autophagy has been implicated and activation of autophagy proposed as a treatment strategy. We generate a human α-synuclein-expressing mouse model of PD with macroautophagic failure in dopamine neurons to understand the interaction between impaired macroautophagy and α-synuclein. We find that impaired macroautophagy generates p62-positive inclusions and progressive neuron loss in the SNc. Despite this parkinsonian pathology, motor phenotypes accompanying human α-synuclein overexpression actually improve with impaired macroautophagy. Real-time fast-scan cyclic voltammetry reveals that macroautophagy impairment in dopamine neurons increases evoked extracellular concentrations of dopamine, reduces dopamine uptake, and relieves paired-stimulus depression. Our findings show that impaired macroautophagy paradoxically enhances dopamine neurotransmission, improving movement while worsening pathology, suggesting that changes to dopamine synapse function compensate for and conceal the underlying PD pathogenesis, with implications for therapies that target autophagy.
AU  - Hunn,BHM
AU  - Vingill,S
AU  - Threlfell,S
AU  - Alegre-Abarrategui,J
AU  - Magdelyns,M
AU  - Deltheil,T
AU  - Bengoa-Vergniory,N
AU  - Oliver,PL
AU  - Cioroch,M
AU  - Doig,NM
AU  - Bannerman,DM
AU  - Cragg,SJ
AU  - Wade-Martins,R
DO  - 10.1016/j.celrep.2019.09.029
EP  - 7
PY  - 2019///
SN  - 2211-1247
SP  - 920
TI  - Impairment of macroautophagy in dopamine neurons has opposing effects on Parkinsonian pathology and behavior
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2019.09.029
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000491881400011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31206-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719312069%3Fshowall%3Dtrue
UR  - http://hdl.handle.net/10044/1/74657
VL  - 29
ER  -
Download