Acrolein-mediated neuronal cell death and alpha-synuclein aggregation: Implication in Parkinson's Disease

In the current investigation using a combination of both in vitro and in vivo testing, coupled with anatomical, functional and behavioral examination, we have presented evidence that acrolein likely plays a critical role in the pathogenesis in the 6-OHDA rat, a typical animal model of Parkinson's Diseases (PD). This is based on the findings that acrolein is elevated in 6-OHDA-injected rats, and behavioral deficits associated with 6-OHDA can be mimicked by injection of acrolein in a similar manner. We also provided evidence that the pathogenic of acrolein in 6-OHDA rats is through the promotion of the oligomerization of alpha-synuclein, the basis of the Lewy body formation, signature pathology in human PD. Hydralazine and Phenelzine, an acrolein scavenger, when applied systemically, can significantly alleviate PD-like motor deficits and dopaminergic cell death in 6-OHDA rats. Such neuroprotection offered by hydralazine and phenelzine in 6-OHDA rats can also be repeated in in vitro experimentation using cell cultures of Dopaminergic and PC-12 cells. These studies are not only indicating a role of acrolein in the pathogenic of PD, but suggesting anti-acrolein therapy as an effective intervention to alleviate tissue damage and motor deficits associated with PD.