Therapeutic Potential of α-Synuclein Evolvability for Autosomal Recessive Parkinson’s Disease

Figure 2

The protective effects of αS against oxidative stress in neuronal cells. (a) αS is shown to protect against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in GT1–7 neuronal cells [22]. αS-expressing, βS-expressing, and vector-transfected cells were treated with hydrogen peroxide (0, 100, 200 μm). At 30 min of treatment, cells were subjected to immunocomplex kinase assay for the assessment of JNK-1 activity. Note. This JNK activity is downregulated in the αS-overexpressing cells compared to other types of cells. In contrast, immunoblot analysis revealed that expression of JNK-interacting protein (JIP)-1, a JNK-phosphatase, was upregulated in the αS-expressing cells. At 24 h, cell survival was determined by the trypan blue exclusion assay and DNA fragmentation assay. Consistent with the results of JNK-1 activity, hydrogen peroxide-treated βS-expressing and vector-transfected but not αS cells displayed DNA fragmentation, as represented by the laddering of genomic DNA. Reprinted from Hashimoto et al. (2002) [22]. (b) In H4 neuroglioma cells treated with hydrogen peroxide, αS was shown to prevent the formation of oxidative stress-induced formation of spherically shaped and hyperpolarized mitochondria, termed “mitospheres,” leading to suppression of apoptosis under the oxidative stress conditions [24]. Reprinted with permission from Menges et al. (2017) [24].

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