Therapeutic Effects of Hydrogen in Animal Models of Parkinson's Disease

Figure 1

Scheme of apoptotic death signaling by accumulation of 8-oxoguanine (8-oxoG; GO) and single-strand-breaks (SSBs) in DNA. ROS, especially hydroxyl radical, increase the 8-oxoG accumulation and SSBs by MUTYH. In the case of SSBs in nucleus, activation of poly (ADP-ribose) polymerase (PARP), apoptosis inducing factor (AIF) translocation from mitochondria to nucleus, and ATP depletion followed by NAD⁺ depletion leads to cellular apoptosis. On the other hands, in mitochondria, accumulation of SSBs induces mitochondrial DNA (mtDNA) degeneration. Loss of function of energy supply leads to ATP depletion, and mitochondrial membrane permeability transition (MMPT), and calpain activation results in lysosomal rupture, which potentiates cell death (modified from Figure  8, Oka et al., 2008 [49]).