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The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications

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Abstract

Glioblastoma multiforme (GBM) grade IV glioma is the most frequent and deadly intracranial cancer. This tumor is determined by unrestrained progression, uncontroled angiogenesis, high infiltration and weak response to treatment, which is chiefly because of abnormal signaling pathways in the tumor. A member related to the Cap ‘n’ collar family of keypart-leucine zipper transcription agents—the transcription factor NF-E2-related factor 2 (Nrf2)-regulates adaptive protection answers by organized upregulation of many genes that produce the cytoprotective factors. In reply to cellular pressures types such as stresses, Nrf2 escapes Kelch-like ECH-related protein 1 (Keap1)-facilitated suppression, moves from the cytoplasm towards the nucleus and performs upregulation of gene expression of antioxidant responsive element (ARE). Nrf2 function is related tocontrolling many types of diseases in the human specially GBM tumor.Thus, we will review the epigeneticalregulatory actions on the Nrf2/Keap1 signaling pathway and potential therapeutic options in GBM by aiming the stimulation of Nrf2.

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Abbreviations

GBM:

Glioblastoma

Keap1:

Kelch-like ECH-related protein 1

Nrf2:

Nuclear factor-erythroid factor 2-related factor 2

ARE:

Antioxidant responsive element

WHO:

World Health Organization

CNS:

Central nervous system

IDH-1:

Isocitrate dehydrogenase 1

PI3K:

Phosphoinositide 3-kinase

RTK:

Receptor tyrosine kinase

MGMT:

O6-methylguanyl DNA methyltransferase

RA:

Retinoic acid

TEM:

Trans-mission electron microscopy

TXNIP:

Thioredoxin-interacting protein 1

EGR1:

Early growth response 1

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Authors and Affiliations

  1. Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Seyed Hossein Shahcheraghi

  2. Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Seyed Hossein Shahcheraghi & Marzieh Lotfi

  3. School of Medicine, Islamic Azad University of Medical Sciences, Yazd, Iran

    Fateme Salemi

  4. Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, Pakistan

    Waqas Alam & Haroon Khan

  5. Harvard Medical School, Boston, MA, USA

    Henry Ashworth

  6. Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, Rome, Italy

    Luciano Saso

  7. Abortion Research Center, Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Marzieh Lotfi

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  1. Seyed Hossein Shahcheraghi
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  2. Fateme Salemi
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Shahcheraghi, S.H., Salemi, F., Alam, W. et al. The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications. Med Oncol 39, 91 (2022). https://doi.org/10.1007/s12032-022-01693-0

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