@report{torre_murazabal_-synuclein_2020,
	title = {α-Synuclein strains influence multiple system atrophy via central and peripheral mechanisms},
	url = {https://biorxiv.org/lookup/doi/10.1101/2020.10.16.342089},
	abstract = {Abstract
          
            Multiple system atrophy ({MSA}) is a progressive neurodegenerative disease with prominent autonomic and motor features. Different disease subtypes are distinguished by their predominant parkinsonian or cerebellar signs. The pathognomonic feature of {MSA} is the presence of α-synuclein (αSyn) protein deposits in glial cells of the central and peripheral nervous system. It is unclear why {MSA}, that invariably presents with αSyn pathology, is clinically so heterogeneous, why it progresses at varying rates and how neuroinflammation affects disease progression. Recently, it was shown that different strains of αSyn can assemble in unique disease environments but also that a variety of strains might exist in the brain of {MSA} patients. We therefore investigated if different αSyn strains might influence {MSA} disease progression. To this aim, we injected two recombinant strains of αSyn in {MSA} transgenic mice and found that they significantly impact {MSA} disease progression in a strain-dependent way via oligodendroglial, neurotoxic and immune-related mechanisms. Neurodegeneration and brain atrophy were accompanied by unique microglial and astroglial responses and the recruitment of central and peripheral immune cells. The differential activation of microglial cells correlated with the structural features of αSyn strains both
            in vitro
            and
            in vivo
            . By injecting αSyn strains in {MSA} mice we could more closely mimic a comprehensive {MSA} phenotype in an experimental setting. This study therefore shows that i) {MSA} phenotype is governed by both the αSyn strain nature and the host environment and ii) αSyn strains can directly trigger a detrimental immune response related to disease progression in {MSA}.},
	institution = {Neuroscience},
	type = {preprint},
	author = {Torre Murazabal, T. and Van der Perren, A. and Coens, A. and Barber Janer, A. and Camacho-Garcia, S. and Stefanova, N. and Melki, R. and Baekelandt, V. and Peelaerts, W.},
	urldate = {2022-02-17},
	date = {2020-10-16},
	langid = {english},
	doi = {10.1101/2020.10.16.342089},
	keywords = {preprint},
}