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ɑ-Synuclein strains and seeding in Parkinson’s disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences

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Abstract

Several age-related neurodegenerative disorders are characterized by the deposition of aberrantly folded endogenous proteins. These proteins have prion-like propagation and amplification properties but so far appear nontransmissible between individuals. Because of the features they share with the prion protein, PrP, the characteristics of pathogenic protein aggregates in several progressive brain disorders, including different types of Lewy body diseases (LBDs), such as Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), have been actively investigated. Even though the pleomorphic nature of these syndromes might suggest different underlying causes, ɑ-synuclein (ɑSyn) appears to play an important role in this heterogeneous group of diseases (the synucleinopathies). An attractive hypothesis is that different types of ɑSyn protein assemblies have a unique and causative role in distinct synucleinopathies. We will discuss the recent research progress on ɑSyn assemblies involved in PD, MSA and DLB; their behavior as strains; current spreading hypotheses; their ability to seed centrally and peripherally; and their implication for disease pathogenesis.

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Funding

Research carried out in the L Bousset and R Melki laboratory is supported by the Centre National de la Recherche Scientifique, European Commission Joint Programme on Neurodegenerative Diseases (JPND-Synaction ANR-15-JPWG-0012-03), The Fondation de France (Contract 2015-00060936), the Fondation Simone et Cino Del Duca of the Institut de France, the Fondation Bettencourt-Schueller, the Fondation Recherche Médicale (Contract DEQ 20160334896) and the Innovative Medicine Initiative 2 Joint grant agreement No 116060 (IMPRiND, www.imprind.org) supported by the European Union’s Horizon 2020 research and innovation program and EFPIA. Research carried out in the Baekelandt laboratory is supported by the FWO Flanders (G.0927.14, G080517N, SBO S006617N Neuro-TRAFFIC), the KU Leuven (OT/14/120), the Fund Sophia 2016-2017, the ERA-NET JPco-fuND 2015 SYNACTION and the Queen Elisabeth Medical Foundation for Neurosciences. WP is a postdoctoral fellow supported by Fulbright, ATCG and Integrated DNA Technologies and FWO Flanders.

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  1. Laboratory for Neurobiology and Gene Therapy, KU Leuven, 3000, Leuven, Belgium

    W. Peelaerts & V. Baekelandt

  2. Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, 49503, USA

    W. Peelaerts

  3. Paris-Saclay Institute of Neuroscience, CNRS, 91190, Gif-sur-Yvette, France

    L. Bousset & R. Melki

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Peelaerts, W., Bousset, L., Baekelandt, V. et al. ɑ-Synuclein strains and seeding in Parkinson’s disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences. Cell Tissue Res 373, 195–212 (2018). https://doi.org/10.1007/s00441-018-2839-5

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