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Protecting dopaminergic neurons from Parkinson’s disease-associated degradation

A defining characteristic of Parkinson’s disease (PD) is the prominent and loss of dopaminergic (DA) neurons within the (SNpc) region of the brain; however, it is not clear why this population of DA neurons is preferentially targeted in PD.

In this issue of the , and colleagues at the National Institute on Aging identified a subpopulation of SNpc DA neurons lacking 1 (ALDH1A1) that are especially prone to degeneration and accumulation of cytotoxic levels of ?-synuclein in a murine model of PD.

Evaluation of PD patient and healthy brains revealed a reduction ALDH1A1 expression and reduced numbers of ALDH1A1-expressing DA neurons in the SNpc of . In PD mice, deletion of Aldh1a1 exacerbated both the loss of DA neurons and ?-synuclein aggregation. Expression of ALDH1A1 in cultured DA neurons from PD mice enhanced cell survival, preventing caspase-mediated cell death. Together, the results from this study suggest that reduced ALDA1A1 expression in PD DA neurons makes this population vulnerable to ?-synuclein-mediated degeneration.

TITLE: Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation


Journal of Clinical Investigation