In vivo models of alpha-synuclein transmission and propagation

Ariadna Recasens, Ayse Ulusoy, Philipp J. Kahle, Donato A. Di Monte, Benjamin Dehay
Cell Tissue Res. 2017-11-29; 373(1): 183-193
DOI: 10.1007/s00441-017-2730-9

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Recasens A(1), Ulusoy A(2), Kahle PJ(3)(4), Di Monte DA(2), Dehay B(5)(6).

Author information:
(1)School of Medical Sciences and Charles Perkins Centre, The University of
Sydney, Camperdown, New South Wales, 2006, Australia.
(2)German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Strasse 27,
53127, Bonn, Germany.
(3)Laboratory of Functional Neurogenetics, Department of Neurodegeneration,
Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen,
(4)German Center of Neurodegenerative Diseases, Tübingen, Germany.
(5)Institut des Maladies Neurodégénératives, UMR 5293, Université de Bordeaux,
33076, Bordeaux, France.
(6)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33076, Bordeaux,

The abnormal accumulation of α-synuclein aggregates in neurons, nerve fibers, or
glial cells is the hallmark of a group of neurodegenerative diseases known
collectively as α-synucleinopathies. Clinical, neuropathological, and
experimental evidence strongly suggests that α-synuclein plays a role not only as
a trigger of pathological processes at disease inception, but also as a mediator
of pathological spreading during disease progression. Specific properties of
α-synuclein, such as its ability to pass from one neuron to another, its tendency
to aggregate, and its potential to generate self-propagating species, have been
described and elucidated in animal models and may contribute to the relentless
exacerbation of Parkinson’s disease pathology in patients. Animal models used for
studying α-synuclein accumulation, aggregation, and propagation are mostly based
on three approaches: (1) intra-parenchymal inoculations of exogenous α-synuclein
(e.g., synthetic α-synuclein fibrils), (2) transgenic mice, and (3) animals (mice
or rats) in which α-synuclein overexpression is induced by viral vector
injections. Whereas pathological α-synuclein changes are consistently observed in
these models, important differences are also found. In particular, pronounced
pathology in transgenic mice and viral vector-injected animals does not appear to
involve self-propagating α-synuclein species. A critical discussion of these
models reveals their strengths and limitations and provides the basis for
recommendations concerning their use for future investigations.


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