The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein
Open accessAbstract
Summary Mutations in α-synuclein and Leucine-rich repeat kinase 2 (LRRK2) are linked to autosomal dominant forms of Parkinson’s disease (PD). However, little is known about any potential pathophysiological interplay between these two PD-related genes. Here we show in transgenic mice that although over-expression of LRRK2 alone did not cause neurodegeneration, the presence of excess LRRK2 greatly accelerated the progression of neuropathological abnormalities developed in PD-related A53T α-synuclein transgenic mice. Moreover, we found that LRRK2 promoted the abnormal aggregation and somatic accumulation of α-synuclein in A53T mice, likely resulted from the impairment of microtubule dynamics, Golgi organization, and ubiquitin-proteasome pathway. Conversely, genetic ablation of LRRK2 preserved the Golgi structure, suppressed the aggregation and somatic accumulation of α-synuclein, and thereby delayed the progression of neuropathology in A53T mice. These findings demonstrate that over-expression of LRRK2 enhances α-synuclein-mediated cytotoxicity and suggest inhibition of LRRK2 expression as a potential therapeutic option for ameliorating α-synuclein-induced neurodegeneration.
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-Synuclein in Parkinson's Disease
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Metadata
- Authors
- Lin, X., Parisiadou, L., Gu, X.-L., Wang, L., Shim, H., Sun, L., Xie, C., Long, C.-X., Yang, W.-J., Ding, J., Chen, Z. Z., Gallant, P. E., Tao-Cheng, J.-H., Rudow, G., Troncoso, J. C., Liu, Z., Li, Z., & Cai, H.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 64
- Issue
- 6
- Pages
- 807-827
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1992483894
- Cited by
- 518
- References
- 9
- FWCI
- 27.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lin, X., Parisiadou, L., Gu, X.-L., Wang, L., Shim, H., Sun, L., Xie, C., Long, C.-X., Yang, W.-J., Ding, J., Chen, Z. Z., Gallant, P. E., Tao-Cheng, J.-H., Rudow, G., Troncoso, J. C., Liu, Z., Li, Z., & Cai, H. (2009). Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein. Neuron. https://doi.org/10.1016/j.neuron.2009.11.006
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