| First Author | Li L | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e85815 |
| PubMed ID | 24392030 | Mgi Jnum | J:211110 |
| Mgi Id | MGI:5574118 | Doi | 10.1371/journal.pone.0085815 |
| Citation | Li L, et al. (2013) Human A53T alpha-synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons. PLoS One 8(12):e85815 |
| abstractText | Parkinson's disease (PD) is the second most common neurodegenerative disease. A key pathological feature of PD is Lewy bodies, of which the major protein component is alpha-synuclein (alpha-syn). Human genetic studies have shown that mutations (A53T, A30P, E46K) and multiplication of the alpha-syn gene are linked to familial PD. Mice overexpressing the human A53T mutant alpha-syn gene develop severe movement disorders. However, the molecular mechanisms of alpha-syn toxicity are not well understood. Recently, mitochondrial dysfunction has been linked with multiple neurodegenerative diseases including Parkinson's disease. Here we investigated whether mitochondrial motility, dynamics and respiratory function are affected in primary neurons from a mouse model expressing the human A53T mutation. We found that mitochondrial motility was selectively inhibited in A53T neurons while transport of other organelles was not affected. In addition, A53T expressing neurons showed impairment in mitochondrial membrane potential and mitochondrial respiratory function. Furthermore, we found that rapamycin, an autophagy inducer, rescued the decreased mitochondrial mobility. Taken together, these data demonstrate that A53T alpha-syn impairs mitochondrial function and dynamics and the deficit of mitochondrial transport is reversible, providing further understanding of the disease pathogenesis and a potential therapeutic strategy for PD. |
