Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
- Michael T. Lin, M. Beal
- BiologyNature
- 19 October 2006
Treatments targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria hold great promise in ageing-related neurodegenerative diseases.
Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease.
- Sonja Kriks, J. Shim, L. Studer
- BiologyNature
- 22 December 2011
A novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo is presented, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells.
Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin.
- Yufeng Yang, S. Gehrke, B. Lu
- BiologyProceedings of the National Academy of Sciences…
- 11 July 2006
It is shown that inhibition of Drosophila Pink1 function results in energy depletion, shortened lifespan, and degeneration of select indirect flight muscles and dopaminergic neurons, and the level of Parkin protein is significantly reduced in dPink1 RNA interference animals.
Mitochondria take center stage in aging and neurodegeneration
- M. Beal
- BiologyAnnals of Neurology
- 1 October 2005
There is strong evidence from genetics and transgenic mouse models that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Alzheimer’s disease, Parkinson's disease, Huntington's Disease, amyotrophic lateral sclerosis, hereditary spastic paraplegia, and cerebellar degenerations.
Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.
- C. Herrnstadt, J. Elson, N. Howell
- BiologyAmerican Journal of Human Genetics
- 1 May 2002
This work used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups.
Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice
- Tiziano Barberi, P. Klivényi, L. Studer
- BiologyNature Biotechnology
- 1 October 2003
A set of coculture conditions is provided that allows rapid and efficient derivation of most central nervous system phenotypes and transplantation of ES and ntES cell–derived dopaminergic neurons corrected the phenotype of a mouse model of Parkinson disease, demonstrating an in vivo application of therapeutic cloning in neural disease.
Functional engraftment of human ES cell–derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes
- N. Roy, C. Cleren, S. K. Singh, Lichuan Yang, M. Beal, S. Goldman
- BiologyNature Network Boston
- 1 November 2006
The utility of recreating the cellular environment of the developing human midbrain while driving dopaminergic neurogenesis from HES cells is shown, and the potential of the resultant cells to mediate substantial functional recovery in a model of Parkinson disease is demonstrated.
Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery
- Yufeng Yang, Y. Ouyang, B. Lu
- BiologyProceedings of the National Academy of Sciences
- 13 May 2008
It is shown that Pink1, a mitochondria-targeted Ser/Thr kinase linked to familial PD, genetically interacts with the mitochondrial fission/fusion machinery and modulates mitochondrial dynamics and is established as a paradigm for PD research.
Mutated Human SOD1 Causes Dysfunction of Oxidative Phosphorylation in Mitochondria of Transgenic Mice*
- M. Mattiazzi, M. D’Aurelio, G. Manfredi
- BiologyJournal of Biological Chemistry
- 16 August 2002
The findings suggest that G93A-mutated hSOD1 in mitochondria may cause mitochondrial defects, which contribute to precipitating the neurodegenerative process in motor neurons.
Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid
- M. Beal, E. Brouillet, B. Hyman
- BiologyJournal of Neuroscience
- 1 October 1993
The effects of intrastriatal, subacute systemic, or chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid in rats showed consistent with in vitro studies showing that mild metabolic compromise can selectively activate NMDA receptors while more severe compromise activates both NMDA and non-NMDA receptors.
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