Title: Alpha-synuclein-induced neurodegeneration is exacerbated in PINK1 knockout mice
Authors: Oliveras Salvá, Marusela ×
Macchi, Francesca
Coessens, Valérie
Deleersnijder, Angélique
Gérard, Melanie
Van der Perren, Anke
Van Den Haute, Chris
Baekelandt, Veerle #
Issue Date: Nov-2014
Publisher: Elsevier
Series Title: Neurobiology of Aging vol:35 issue:11 pages:2625-36
Article number: S0197-4580(14)00408-4
Abstract: Loss-of-function mutations in the PINK1 gene lead to recessive forms of Parkinson's disease. Animal models with depleted PINK1 expression have failed to reproduce significant nigral dopaminergic neurodegeneration and clear alpha-synuclein pathology, main characteristics of the disease. In this study, we investigated whether alpha-synuclein pathology is altered in the absence of PINK1 in cell culture and in vivo. We observed that downregulation of PINK1 enhanced alpha-synuclein aggregation and apoptosis in a neuronal cell culture model for synucleinopathy. Silencing of PINK1 expression in mouse substantia nigra using recombinant adeno-associated viral vectors did not induce dopaminergic neurodegeneration in a long-term study up to 10 months, nor did it enhance or accelerate dopaminergic neurodegeneration after alpha-synuclein overexpression. However, in PINK1 knockout mice, overexpression of alpha-synuclein in the substantia nigra resulted in enhanced dopaminergic neurodegeneration as well as significantly higher levels of alpha-synuclein phosphorylation at serine 129 at 4 weeks postinjection. In conclusion, our results demonstrate that total loss of PINK1 leads to an increased sensitivity to alpha-synuclein-induced neuropathology and cell death in vivo.
ISSN: 0197-4580
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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