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Global Translational Medicine Influence of ferroptosis in neurological diseases

A B

Figure 7. Therapeutic drugs and miRNA that might target ferroptotic transcription factors (FerrTFs) for Alzheimer’s disease (AD). (A) 681 drugs that
might be therapeutic against 8 FerrTFs for AD. (B) 126 miRNAs that might silence 7 FerrTFs against AD.

this notion, as ferroptosis has been shown to influence associated mutant p53 and the signaling system linked with
lipid synthesis and metabolic pathways . Therefore, the p53 can control ferroptosis . In our study, we found that
[67]
[51]
disruption of lipid metabolism by ferroptosis may contribute p53 targets the maximum number of hubs from different
to the progressive neurodegeneration in AD. clusters of the PD PPIN, and 3 out of 7 of its TGs were from
cluster 10, which was functionally enriched with the GO BP
Existing literature suggests that dysregulation of – “regulation of I-κB kinase/NF-κB cascade.” The targets
NF-κB signaling can lead to apoptosis, inflammation, and of p53 in this cluster include CASP1, NLRC4, and CHUK.
the progression of several neurodegenerative diseases, p53 aggravates the expression of NLRC4, and the role of
including PD . Strikingly, several components of the NLRC4 in PD has been elucidated earlier in this discussion.
[63]
NF-κB signaling cascade, such as IRF7, NLRC4, CHUK, CHUK encodes IKKα, an important tumor suppressor for
and CASP1, are regulated by FerrTFs (Figure 6). NLRC4 has suppressing the inflammatory NF-κB pathway within the
been reported to cause neuroinflammation and promote cell . However, in our study, p53 was found to suppress
[68]
PD . Among the FerrTFs, TP53 encodes tumor protein the expression of CHUK, potentially exacerbating NF-κB-
[64]
p53, which was found to be upregulated in dopaminergic mediated inflammatory pathways. Moreover, TP53 was
neurons of the substantia nigra pars compacta in PD also found to regulate the expression of the hub for cluster
brains . The loss of dopaminergic neurons in this brain 13, namely STAT1. This cluster was functionally enriched
[65]
[65]
region is a hallmark of PD progression . p53, along with with GO BP – “Positive regulation of immune system
NF-κB, has been shown to contribute to the progressive process.” It has been reported that the interaction of STAT1
degradation of dopaminergic neurons in the PD brain . and NF-κB is responsible for bringing about inflammatory
[66]
Recent research has demonstrated that both tumor- responses . Strikingly, ferroptosis aggravates pro-
[69]
Volume 2 Issue 3 (2023) 9 https://doi.org/10.36922/gtm.0318