The Alpha-Synuclein RT-QuIC Products Generated by the Olfactory Mucosa of Patients with Parkinson’s Disease and Multiple System Atrophy Induce Inflammatory Responses in SH-SY5Y Cells

Cells

Roberto Eleopra¹  Alessandra Consonni²  Fulvio Baggi²  Giuseppe Bufano³  Giorgio Giaccone³  Chiara Maria Giulia De Luca³  Fabio Moda³  Federico Angelo Cazzaniga³  Edoardo Bistaffa³  Giorgia Quitarrini³  Giuseppe Legname⁴  Luigi Celauro⁴ 

[1] Division of Neurology 1, Parkinson and Movement Disorders, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy;Division of Neurology 4, Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy;Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy;Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore Di Studi Avanzati (SISSA), 34136 Trieste, Italy;

关键词: RT-QuIC;    olfactory mucosa;    α-synuclein;    Parkinson’s disease;    multiple system atrophy;    strains;   

DOI  :  10.3390/cells11010087

来源: DOAJ

【 摘 要 】

Parkinson’s disease (PD) and multiple system atrophy (MSA) are caused by two distinct strains of disease-associated α-synuclein (αSyn^D). Recently, we have shown that olfactory mucosa (OM) samples of patients with PD and MSA can seed the aggregation of recombinant α-synuclein by means of Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC). Remarkably, the biochemical and morphological properties of the final α-synuclein aggregates significantly differed between PD and MSA seeded samples. Here, these aggregates were given to neuron-like differentiated SH-SY5Y cells and distinct inflammatory responses were observed. To deepen whether the morphological features of α-synuclein aggregates were responsible for this variable SH-SY5Y inflammatory response, we generated three biochemically and morphologically distinct α-synuclein aggregates starting from recombinant α-synuclein that were used to seed αSyn_RT-QuIC reaction; the final reaction products were used to stimulate SH-SY5Y cells. Our study showed that, in contrast to OM samples of PD and MSA patients, the artificial aggregates did not transfer their distinctive features to the αSyn_RT-QuIC products and the latter induced analogous inflammatory responses in cells. Thus, the natural composition of the αSyn^D strains but also other specific factors in OM tissue can substantially modulate the biochemical, morphological and inflammatory features of the αSyn_RT-QuIC products.

【 授权许可】

Unknown