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Aldehyde dehydrogenase 1 determines the regional selectivity of nigral dopaminergic neuron loss in Parkinson’s disease

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J. Yu
  • J.H. Ding
  • C.S. Xie
  • L.X Sun
  • G. Rudow
  • H.B. Cai


Parkinson’s disease (PD), the most common degenerative movement disorder, is pathologically characterized by a preferential loss of nigral dopaminergic (DA) neurons(1). While less is known about the regional selectivity of nigral DA neuron loss within the substantia nigra pas compacta (SNpc), of which the underlying molecular mechanism is completely obscure. We recently generated a new line of alpha-synuclein transgenic mice by conditional expression of PD-related alpha-synuclein A53T missense mutation in the midbrain DA neurons. The resulting mutant mice developed profound motor disabilities as well as robust and progressive loss of nigral DA neurons. Aldehyde dehydrogenase 1 (ALDH1A1) is specifically expressed by a subpopulation of nigral DA neurons located in the ventrolateral(VL) tier of rodent SNpc. Here we found that the ALDH1A1-expressing nigral DA neurons were more resistant to alpha-syn-mediated neurodegeneration compared to the ALDH1A1-lacking nigral DA neurons in the alpha-synuclein transgenic mice. Furthermore, genetic ablation of ALDH1A1 exacerbated the degeneration of nigral DA neurons in these mice. Our findings establish ALDH1A1 as a key molecular determinant of the regional vulnerability of nigral DA neurons in PD, suggesting that ALDH1A1 may play a protect role against nigral neurodegeneration.

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