The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Elevated Mitochondrial Bioenergetics and Axonal Arborization Size Are Key Contributors to the Vulnerability of Dopamine Neurons
Open accessAbstract
Although the mechanisms underlying the loss of neurons in Parkinson's disease are not well understood, impaired mitochondrial function and pathological protein aggregation are suspected as playing a major role. Why DA (dopamine) neurons and a select small subset of brain nuclei are particularly vulnerable to such ubiquitous cellular dysfunctions is presently one of the key unanswered questions in Parkinson's disease research. One intriguing hypothesis is that their heightened vulnerability is a consequence of their elevated bioenergetic requirements. Here, we show for the first time that vulnerable nigral DA neurons differ from less vulnerable DA neurons such as those of the VTA (ventral tegmental area) by having a higher basal rate of mitochondrial OXPHOS (oxidative phosphorylation), a smaller reserve capacity, a higher density of axonal mitochondria, an elevated level of basal oxidative stress, and a considerably more complex axonal arborization. Furthermore, we demonstrate that reducing axonal arborization by acting on axon guidance pathways with Semaphorin 7A reduces in parallel the basal rate of mitochondrial OXPHOS and the vulnerability of nigral DA neurons to the neurotoxic agents MPP(+) (1-methyl-4-phenylpyridinium) and rotenone. Blocking L-type calcium channels with isradipine was protective against MPP(+) but not rotenone. Our data provide the most direct demonstration to date in favor of the hypothesis that the heightened vulnerability of nigral DA neurons in Parkinson's disease is directly due to their particular bioenergetic and morphological characteristics.
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233
Metabolic control through the PGC-1 family of transcription coactivators
Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130 · cited 1×
“We used qPCR to examine the level of expression of PGC-1a (peroxisome proliferator-activated receptor g coactivator), a well-known regulator of mitochondrial function and biogenesis [15].”
MethodSynaptic Energy Use and Supply
Harris, J. J., Jolivet, R., & Attwell, D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.019 · Cited by 1,747
Oxidative Pathways for Catecholamines in the Genesis of Neuromelanin and Cytotoxic Quinones
GRAHAM, D. G. (1978) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13535-9 · Cited by 1,126 · cited 1×
“However, our results do not exclude that, in addition, other sources of ROS such as those arising from the oxidative metabolism of DA itself [32] could also play a role.”
ResultZong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036
‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease
Chan, C. S., Guzman, J. N., Ilijic, E., Mercer, J. N., Rick, C., Tkatch, T., Meredith, G. E., & Surmeier, D. J. (2007) · Nature · doi:10.1038/nature05865 · Cited by 904
Matsuda, W., Furuta, T., Nakamura, K. C., Hioki, H., Fujiyama, F., Arai, R., & Kaneko, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4029-08.2009 · Cited by 865
Cited by
Selective neuronal vulnerability in Parkinson disease
Surmeier, D. J., Obeso, J. A., & Halliday, G. M. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.178 · Cited by 1,116
Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand
McWilliams, T. G., Prescott, A. R., Montava-Garriga, L., Ball, G., Singh, F., Barini, E., Muqit, M. M. K., Brooks, S. P., & Ganley, I. G. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.008 · Cited by 591
Ge, P., Dawson, V. L., & Dawson, T. M. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00367-7 · Cited by 496
Determinants of dopaminergic neuron loss in Parkinson's disease
Surmeier, D. J. (2018) · The FEBS Journal · doi:10.1111/febs.14607 · Cited by 444
Mitochondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential
Henrich, M. T., Oertel, W. H., Surmeier, D. J., & Geibl, F. F. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00676-7 · Cited by 406
Metadata
- Authors
- Pacelli, C., Giguère, N., Bourque, M.-J., Lévesque, M., Slack, R. S., & Trudeau, L.-É.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 25
- Issue
- 18
- Pages
- 2349-2360
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1698967089
- Cited by
- 530
- References
- 53
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pacelli, C., Giguère, N., Bourque, M.-J., Lévesque, M., Slack, R. S., & Trudeau, L.-É. (2015). Elevated Mitochondrial Bioenergetics and Axonal Arborization Size Are Key Contributors to the Vulnerability of Dopamine Neurons. Current Biology. https://doi.org/10.1016/j.cub.2015.07.050
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