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@article{Perni:2021:10.3389/fcell.2021.552549,
author = {Perni, M and van, der Goot A and Limbocker, R and van, Ham TJ and Aprile, FA and Xu, CK and Flagmeier, P and Thijssen, K and Sormanni, P and Fusco, G and Chen, SW and Challa, PK and Kirkegaard, JB and Laine, RF and Ma, KY and Muller, MBD and Sinnige, T and Kumita, JR and Cohen, SIA and Seinstra, R and Kaminski, Schierle GS and Kaminski, CF and Barbut, D and De, Simone A and Knowles, TPJ and Zasloff, M and Nollen, EAA and Vendruscolo, M and Dobson, CM},
doi = {10.3389/fcell.2021.552549},
journal = {Frontiers in Cell and Developmental Biology},
pages = {1--10},
title = {Comparative studies in the A30P and A53T alpha-Synuclein C. elegans strains to investigate the molecular origins of Parkinson's Disease},
url = {http://dx.doi.org/10.3389/fcell.2021.552549},
volume = {9},
year = {2021}
}

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TY  - JOUR
AB  - The aggregation of α-synuclein is a hallmark of Parkinson's disease (PD) and a variety of related neurological disorders. A number of mutations in this protein, including A30P and A53T, are associated with familial forms of the disease. Patients carrying the A30P mutation typically exhibit a similar age of onset and symptoms as sporadic PD, while those carrying the A53T mutation generally have an earlier age of onset and an accelerated progression. We report two C. elegans models of PD (PDA30P and PDA53T), which express these mutational variants in the muscle cells, and probed their behavior relative to animals expressing the wild-type protein (PDWT). PDA30P worms showed a reduced speed of movement and an increased paralysis rate, control worms, but no change in the frequency of body bends. By contrast, in PDA53T worms both speed and frequency of body bends were significantly decreased, and paralysis rate was increased. α-Synuclein was also observed to be less well localized into aggregates in PDA30P worms compared to PDA53T and PDWT worms, and amyloid-like features were evident later in the life of the animals, despite comparable levels of expression of α-synuclein. Furthermore, squalamine, a natural product currently in clinical trials for treating symptomatic aspects of PD, was found to reduce significantly the aggregation of α-synuclein and its associated toxicity in PDA53T and PDWT worms, but had less marked effects in PDA30P. In addition, using an antibody that targets the N-terminal region of α-synuclein, we observed a suppression of toxicity in PDA30P, PDA53T and PDWT worms. These results illustrate the use of these two C. elegans models in fundamental and applied PD research.
AU  - Perni,M
AU  - van,der Goot A
AU  - Limbocker,R
AU  - van,Ham TJ
AU  - Aprile,FA
AU  - Xu,CK
AU  - Flagmeier,P
AU  - Thijssen,K
AU  - Sormanni,P
AU  - Fusco,G
AU  - Chen,SW
AU  - Challa,PK
AU  - Kirkegaard,JB
AU  - Laine,RF
AU  - Ma,KY
AU  - Muller,MBD
AU  - Sinnige,T
AU  - Kumita,JR
AU  - Cohen,SIA
AU  - Seinstra,R
AU  - Kaminski,Schierle GS
AU  - Kaminski,CF
AU  - Barbut,D
AU  - De,Simone A
AU  - Knowles,TPJ
AU  - Zasloff,M
AU  - Nollen,EAA
AU  - Vendruscolo,M
AU  - Dobson,CM
DO  - 10.3389/fcell.2021.552549
EP  - 10
PY  - 2021///
SN  - 2296-634X
SP  - 1
TI  - Comparative studies in the A30P and A53T alpha-Synuclein C. elegans strains to investigate the molecular origins of Parkinson's Disease
T2  - Frontiers in Cell and Developmental Biology
UR  - http://dx.doi.org/10.3389/fcell.2021.552549
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000636575500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.frontiersin.org/articles/10.3389/fcell.2021.552549/full
UR  - http://hdl.handle.net/10044/1/88078
VL  - 9
ER  -

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