Imperial College London
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ProfessorAlfonsoDe Simone

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3052a.de-simon Website

 
 
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Location

 

603Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Boi:2020:10.3390/ijms21228535,
author = {Boi, L and Pisanu, A and Fusco, G and Carboni, E and Casu, MA and Satta, V and Scherma, M and Janda, E and Palmas, MF and Mocci, I and Ena, A and Mulas, G and Spiga, S and Fadda, P and De, Simone A and Carta, A},
doi = {10.3390/ijms21228535},
journal = {International Journal of Molecular Sciences},
title = {Modeling Parkinson’s disease neuropathology and symptoms by  intranigral inoculation of preformed human α-synuclein oligomers},
url = {http://dx.doi.org/10.3390/ijms21228535},
volume = {21},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson’s disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies.
AU  - Boi,L
AU  - Pisanu,A
AU  - Fusco,G
AU  - Carboni,E
AU  - Casu,MA
AU  - Satta,V
AU  - Scherma,M
AU  - Janda,E
AU  - Palmas,MF
AU  - Mocci,I
AU  - Ena,A
AU  - Mulas,G
AU  - Spiga,S
AU  - Fadda,P
AU  - De,Simone A
AU  - Carta,A
DO  - 10.3390/ijms21228535
PY  - 2020///
SN  - 1422-0067
TI  - Modeling Parkinson’s disease neuropathology and symptoms by  intranigral inoculation of preformed human α-synuclein oligomers
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms21228535
UR  - http://hdl.handle.net/10044/1/85371
VL  - 21
ER  -
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