With ATH434 PD patients ( in the future) will get rid of iron by "redistributing loosely bound excess iron in brain", as told by Stamler in his presentations.
There is earlier evidence that iron promotes alpha-synuclein aggregation and causes oxidative stress causing cell damage and neuroinflammation also presented by Stamler in his talks.
The new issue in this Chinese paper below there is evidence of how excess iron inhibits autophagy and how this will result in fewer dopamine neurons.
Seems to be a free paper, here is the abstract.

J Cell Mol Med

. 2023 Sep 5.

doi: 10.1111/jcmm.17946. Online ahead of print.

Iron-inhibited autophagy via transcription factor ZFP27 in Parkinson's disease

Yinying Wang ¹, Qian Wen ², Rongsha Chen ¹, Zhichao Gan ², Xinwei Huang ¹, Pengfei Wang ¹, Xia Cao ¹, Ninghui Zhao ², Zhongshan Yang ³, Jinyuan Yan ¹

Affiliations expand

• PMID: 37668106

DOI: 10.1111/jcmm.17946

Abstract

Parkinson's disease (PD) is a challenge because of the ageing of the population and the disease's complicated pathogenesis. Accumulating evidence showed that iron and autophagy were involved in PD. Nevertheless, the molecular mechanism and role of iron and autophagy in PD are not yet elucidated. In the present study, it was shown that PD mice had significant motor dysfunction, increased iron content, less dopamine neurons and more α-synuclein accumulation in the substantia nigra. Meanwhile, PD mice treated with deferoxamine exhibited less iron content, relieved the dyskinesia and had a significant increase in dopamine neurons and a significant decrease in α-synuclein. Autophagy induced by LC3 was inhibited in PD models with iron treatment. Following verification showed that iron aggregation restrained insulin-like growth factor 2 (IGF2) and transcription factor zinc finger protein 27 (ZFP27) in PD models. In addition, LC3-induced autophagy flux was reduced with ZFP27 knockdown. Furthermore, ZFP27 affected autophagy by regulating LC3 promoter activity. These data suggest that iron deposition inhibits IGF2 and ZFP27 to reduce LC3-induced autophagy, and ultimately decrease dopamine neurons, accelerating PD progression. Our findings provide a novel insight that ZFP27-mediated iron-related autophagy and IGF2 may activate the downstream kinase gene to trigger autophagy in the PD model.