Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice

By Kelvin C. Luk, Victoria M. Kehm, Bin Zhang, Patrick O’Brien, John Q. Trojanowski, V. Lee. Journal of Experimental Medicine, 2012

1,011 citations recorded by the source corpus.

Synthetic a-Synuclein fibrils injected into the brain spread far beyond the injection site and are sufficient to accelerate Parkinson’s disease–like pathology in mice.

Subfields: Cellular and Molecular Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/e6f4aabc898e6d55de85eb4143829179975106e3

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Citations in the corpus

A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles (2014, background): “Secretion and cell-to-cell transfer of a-synuclein has been shown both in cells and in vivo (Lee et al, 2004, 2005, 2008a,b; Desplats et al, 2009; Luk et al, 2012a,b), and exosomes constitute a proposed method of propagation (Emmanouilidou et al, 2010; Kong et al, 2014; Lee et al, 2014).”
Mitochondrial Dysfunction in Neurodegenerative Diseases (2012, background): “…to neurodegenerative diseases with genetic experiments providing convincing evidence that mutant A␤, ␣-synuclein, and tau can be transferred between neighboring neurons, and then induce pathological changes in these neurons (Harris et al., 2010; Luk et al., 2012; de Calignon et al., 2012).”
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, positive): “…mice, intra-cerebral injection of brain homogenates from older symptomatic transgenic mice accelerates a -synuclein aggregation and neuronal degeneration, even at regions far beyond injection sites, a phenomenon also observed after injection of synthetic a -synuclein ﬁbrils (Luk et al , 2012).”
Prion-like spreading of pathological α-synuclein in brain (2013, background): “Luk et al. (2012a) showed that only inoculation of synthetic mouse -synuclein fibrils into wild-type mouse brain induced synuclein pathology.”
Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism (2015, background): “Subsequently, α-synuclein prions were shown to arise spontaneously in TgM83 mice expressing mutant human α-synuclein by three separate groups (13, 40, 41).”