This paper tells how iron overload hampers microglia which is closely related to neurodegeneration. The paper is not free to read but we can read it partially.

In the discussion, the last sentence tells: " In fact, evidences show that excessive iron will increase catalytic iron and play a key role in the pathogenesis of many diseases, such as diabetes, cirrhosis and tumorigenesis (Jahng et al., 2019). Due to the accumulation of iron in the process of healthy aging, iron imbalance may play an important role in the occurrence of several...."

So we need to guess the rest of this discussion, but in any case, I feel that ATH434, a safe iron chelator (?), has a lot of value in helping to reduce the iron overload in many diseases and not only in neurodegenerative problems but also in many other old age medical problems.

Food Chem Toxicol

. 2023 Sep 28;114054.

doi: 10.1016/j.fct.2023.114054. Online ahead of print.

Iron blocks autophagic flux and induces autophagosomes accumulation in microglia

Deqiang Fu ¹, Xingyue Liang ², Yuxuan Jiang ³, Jieping Liu ³, Xiaosi Lin ³, Quan Yang ³, Xue Chen ³, Ping Huang ³, Wei Wang ⁴, Wenlin Wu ⁵

Affiliations expand

• PMID: 37777083

DOI: 10.1016/j.fct.2023.114054

Abstract

Iron is an essential dietary micronutrient for maintaining physiological homeostasis. However, disruption of cerebral iron regulation with the accumulation of iron in different brain structures appears to have a role in the pathogenesis of various neurodegenerative disorders. Studies have reported that autophagy induction could potentially mitigate progression in neurodegenerative diseases with iron deposition, but the relationship between autophagy and iron remains poorly understood. Meanwhile, abnormal autophagy in microglia is closely related to the occurrence of neurodegenerative diseases. Therefore, the effect of iron on microglia autophagy needs to be elaborated. In the present study, we found that iron induces autophagosome accumulation but inhibits its initiation in an Akt-mTOR pathway independent manner. Meanwhile, it caused autophagy flux defects and dysfunction of lysosomes. We also found that iron overload reduced the expression of Rab7, which is an essential protein for the fusion of autophagosomes and lysosomes. These results suggest that iron induces the accumulation of autophagosome in microglia and disrupts the autophagic flux in late stage of autophagy. Therefore, our work provides new insights into the molecular mechanisms of iron neurotoxicity.