Phase1 may demonstrate target engagement, page-16

Pivalde, I think the proven ability of PBT434 to up-regulate DJ-1 suggest it is active in the mitochondria. DJ-1 can also combine with the protein P53 ( the protector of the genome) for a positive effect.
[ It was also found that DJ-1 bound to p53 in vitro and in vivo and that colocalization with and its binding to p53 were stimulated by UV irradiation of cells. Transcription activity of p53 was found to be abrogated by Topors concomitant with sumoylation of p53 in a dose-dependent manner, and DJ-1 restored its repressed activity by releasing the sumoylated form of p53. These findings suggest that DJ-1 positively regulates p53 through Topors-mediated sumoylation.]
(UV to damage DNA)
https://www.ncbi.nlm.nih.gov/pubmed/15703819/

[p53 pathway: In a normal cell, p53 is inactivated by its negative regulator, mdm2. Upon DNA damage or other stresses, various pathways will lead to the dissociation of the p53 and mdm2 complex. Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell or apoptosis to discard the damaged cell. How p53 makes this choice is currently unknown.]
https://en.wikipedia.org/wiki/P53
It looks like PBT434 not only helps through up-regulation of DJ-1, but also by eliminating excess iron from cells, known to drive aggregation which deactivates P53.

[p53 is a master regulatory protein that participates in cellular processes such as apoptosis, DNA repair, and cell cycle control. p53 functions as a homotetrameric tumor suppressor, and is lost in more than 50% of human cancers. Recent studies have suggested that the formation of mutant p53 aggregates is associated with loss-of-function (LoF), dominant-negative (DN), and gain-of-function (GoF) effects. We propose that these phenomena can be explained by a prion-like behavior of mutant p53. We discuss the shared properties of cancer and neurodegenerative diseases and how the prion-like properties of p53 aggregates offer potential targets for drug development.]
https://www.ncbi.nlm.nih.gov/pubmed/24775734

Obviously by protecting DNA, P53 is a cancer suppressor, with about 50% of cancers caused by loss of P53 function. I found this info from cancer researchers.
[ To the best of our knowledge, this is the first report suggesting the role of p53 in the maintenance of metal ion homeostasis in vivo. However, systemic iron homeostasis is regulated by multiple mechanisms including intestinal iron uptake, iron exporter ferroportin, and iron consumption in the body. ]
https://www.nature.com/articles/srep16497