Iron, central in the PD pathology,

Iron as the concertmaster in the pathogenic orchestra playing in sporadic Parkinson’s disease | SpringerLink

This paper tells "everything" how iron plays a central role in PD pathology. So it is a good paper to read if you want to understand why iron chelation by ATH434 could work in helping PD patients. It is not written by the top scientist of neurodegeneration but it tells IMO the most central issues.

The halfway conclusions were:

• IRON increases with age.

• IRON transfer through BBB is increased.

• IRON export from brain is increased.

• IRON is increased in SN blood vessels.

• IRON storage by ferritin and neuromelanin is dysregulated.

• Free/labile IRON increases and induces Fenton reaction leading to toxic hydroxyl radicals.

• Ferroptosis causes proteasomal defect, mitochondrial disturbances and cellular cytotoxic processes, lysosomal defects, apoptosis and autophagy dysregulation, all together causing cell degeneration. Ferroptosis is characterized by an accumulation of lipid hydroperoxides (Dixon Scott et al. 2012). The sensitivity to ferroptosis is linked to numerous biological processes and in particular to iron, glutathione, phospholipid, NADPH, coenzyme Q₁₀ and polyunsaturated fatty acid metabolism (Yan and Zhang 2020; Stockwell et al. 2017). A deficient regulation of ferroptosis has been found in MPTP-treated mice (Tapias 2019), a model of PD pathology (Fig. 3).
  
  But there is more when you continue after these conclusions including a very long list of references.
  It is easy to agree with the final conclusions in the abstract:
  "iron" is a major player in the pathology of PD. Selective chelation of excess iron at the site of the substantia nigra, where a dysfunction of the BBB is suggested, with peripherally acting iron chelators is suggested to contribute to the portfolio and therapeutic armamentarium of anti-Parkinson medications.
  
  Now ATH needs to present that ATH434 works also in human PD. I would think that the primate study will come before that and most likely it is already going on somewhere.