bims-redobi Biomed News
on Redox biology
Issue of 2024–10–06
two papers selected by
Vanesa Cepas López, Candiolo Cancer Institute
  1. Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.
  2. Cisplatin-Induces Kidney Damage through the Down-Regulation of Prx I by Autophagic Degradation.
  1. Curr Drug Targets. 2024 Sep 27.
    Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.
    Maneesh Mohan, Ashi Mannan, Chirag Kakkar, Thakur Gurjeet Singh.
      Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.
    Keywords:  Nrf2; ferroptosis; mechanistic pathways.; neurological diseases; oxidative stress; therapeutic pathway
    DOI:  https://doi.org/10.2174/0113894501320839240918110656
  2. Free Radic Biol Med. 2024 Oct 02. pii: S0891-5849(24)00696-8. [Epub ahead of print]
    Cisplatin-Induces Kidney Damage through the Down-Regulation of Prx I by Autophagic Degradation.
    Jiyoung Park, Juhyun Sim, Ho Jin Yi, Sue Goo Rhee, Hyun Ae Woo.
      In this study, we investigated the potential role of PrxI in cis-diamminedichloroplatinum (cisplatin)-induced renal damage in mice. The anticancer drug cisplatin is a chemotherapeutic agent that is widely used to treat solid tumors. Cisplatin-induced nephrotoxicity is a serious dose-limiting side effect, primarily caused by oxidative stress. The oxidative stress further damages DNA, membranes, and mitochondria, and increases endoplasmic reticulum (ER) stress. Cisplatin produces reactive oxygen species (ROS) through Cytochrome P450 2E1 (CYP2E1) and localizes to the surface of the ER, where CYP2E1 is located. Among the six Prx isoforms, Prx I was selectively degraded in cisplatin-treated kidneys during severe renal function damage. Prx I degradation is blocked in mouse proximal tubular cells treated with 3-methyladenine, an autophagy inhibitor, and in MEF lacking ATG7. Moreover, increased ROS levels on the ER surface due to CYP2E1 overexpression further accelerated Prx I degradation. These results suggest that Prx I degradation is largely mediated through autophagy, which is promoted by cisplatin-induced ER stress. Ablation of Prx I exacerbated cisplatin-induced nephrotoxicity and significantly increased the abundance of oxidative stress, ER stress, and inflammatory markers in the kidney, indicating that Prx I plays a protective role against cisplatin-induced nephrotoxicity.
    Keywords:  Autophagy; Cisplatin; ER stress; Nephrotoxicity; Peroxiredoxin I
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.09.049
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