A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases
Author:
Mandemakers Wim1, Morais Vanessa A.1, De Strooper Bart1
Affiliation:
1. Center for Human Genetics, K.U.Leuven and Department of Molecular and Developmental Genetics, VIB, Herestraat 49, 3000 Leuven, Belgium
Abstract
Dysfunction of mitochondria is frequently proposed to be involved in neurodegenerative disease. Deficiencies in energy supply, free radical generation, Ca2+ buffering or control of apoptosis, could all theoretically contribute to progressive decline of the central nervous system. Parkinson disease illustrates how mutations in very different genes finally impinge directly or indirectly on mitochondrial function, causing subtle but finally fatal dysfunction of dopaminergic neurons. Neurons in general appear more sensitive than other cells to mutations in genes encoding mitochondrial proteins. Particularly interesting are mutations in genes such as Opa1, Mfn1 and Dnm1l, whose products are involved in the dynamic morphological alterations and subcellular trafficking of mitochondria. These indicate that mitochondrial dynamics are especially important for the long-term maintenance of the nervous system. The emerging evidence clearly demonstrates the crucial role of specific mitochondrial functions in maintaining neuronal circuit integrity.
Publisher
The Company of Biologists
Reference151 articles.
1. Abbas, N., Lucking, C. B., Ricard, S., Durr, A., Bonifati, V., De Michele, G., Bouley, S., Vaughan, J. R., Gasser, T., Marconi, R. et al. (1999). A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease. Hum. Mol. Genet.8, 567-574. 2. Abeliovich, A., Schmitz, Y., Farinas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., Shinsky, N., Verdugo, J. M., Armanini, M., Ryan, A. et al. (2000). Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron25, 239-252. 3. Autere, J., Moilanen, J. S., Finnila, S., Soininen, H., Mannermaa, A., Hartikainen, P., Hallikainen, M. and Majamaa, K. (2004). Mitochondrial DNA polymorphisms as risk factors for Parkinson's disease and Parkinson's disease dementia. Hum. Genet.115, 29-35. 4. Bae, B. I., Xu, H., Igarashi, S., Fujimuro, M., Agrawal, N., Taya, Y., Hayward, S. D., Moran, T. H., Montell, C., Ross, C. A. et al. (2005). p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron47, 29-41. 5. Bandopadhyay, R., Kingsbury, A. E., Cookson, M. R., Reid, A. R., Evans, I. M., Hope, A. D., Pittman, A. M., Lashley, T., Canet-Aviles, R., Miller, D. W. et al. (2004). The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease. Brain127, 420-430.
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