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Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation
Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11–16 years) developed α-synuclein–positive Lewy bodies in grafted neurons, providing the first evidence, to the authors' knowledge, that the disease can propagate from host to graft cells.
α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells.
In vivo transfer of α-syn between host cells and grafted dopaminergic neurons in mice overexpressing human α- syn and results suggest that α- Syn propagation is a key element in the progression of Parkinson disease pathology.
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats
The first experimental evidence that different α-synuclein forms can propagate from the gut to the brain is provided, and that microtubule-associated transport is involved in the translocation of aggregated α- synuclein in neurons is provided.
Transplantation of Human Embryonic Stem Cell‐Derived Cells to a Rat Model of Parkinson's Disease: Effect of In Vitro Differentiation on Graft Survival and Teratoma Formation
Investigation of the effect of in vitro predifferentiation on in vivo survival and differentiation of hESCs implanted into the 6‐OHDA (6‐hydroxydopamine)‐lesion rat model of PD indicates that prolonged in vitro differentiation ofhESCs is essential for preventing formation of teratomas.
Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice
The R6/2 transgenic mouse model of Huntington's disease develops diabetes due to deficient beta-cell mass and exocytosis.
Diabetes in R6/2 mice is caused by a combination of deficient beta-cell mass and disrupted exocytosis, which could be attributed to a 96% reduction in the number of insulin-containing secretory vesicles.
Neurogenin2 Directs Granule Neuroblast Production and Amplification while NeuroD1 Specifies Neuronal Fate during Hippocampal Neurogenesis
- L. Roybon, T. Hjalt, Simon R W Stott, F. Guillemot, Jia-Yi Li, P. Brundin
- Biology, PsychologyPloS one
- 10 March 2009
A critical role is demonstrated for Ngn2 and NeuroD1 in controlling neuronal commitment and hippocampal granule neuroblast formation, both during embryonic development and in post-natal hippocampalgranule neurogenesis.
Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain
- Wen Li, E. Englund, Jia-Yi Li
- Biology, MedicineProceedings of the National Academy of Sciences
- 2 May 2016
The postmortem analysis of a patient with Parkinson’s disease who underwent unilateral cell transplantation in the putamen with human embryonic mesencephalic tissue at 24 y before death provides the first reported evidence that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.
Neuronal Properties, In Vivo Effects, and Pathology of a Huntington's Disease Patient‐Derived Induced Pluripotent Stem Cells
Results indicate that, although HD‐iPSC carrying 72 CAG repeats can form GABAergic neurons and give rise to functional effects in vivo, without showing an overt HD phenotype, it is highly susceptible to proteasome inhibition and develops HD pathology at later stages of transplantation.
Cholinergic neuronal defect without cell loss in Huntington's disease.
The data show that the cholinergic system is dysfunctional in R6/1 and HD patients, and provide a rationale for testing of pro-cholinergic drugs in this disease.