A Pivotal Role of Nrf2 in Neurodegenerative Disorders: A New Way for Therapeutic Strategies

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SÜZEN S., Tucci P., Profumo E., Buttari B., Saso L.

PHARMACEUTICALS, cilt.15, sa.6, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 15 Sayı: 6
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/ph15060692
  • Dergi Adı: PHARMACEUTICALS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: Alzheimer's disease, Huntington's disease, Parkinson's disease, ALS, Nrf2, oxidative stress, antioxidant, neurodegenerative, AMYOTROPHIC-LATERAL-SCLEROSIS, ANTIOXIDANT RESPONSE ELEMENT, TRANSCRIPTION FACTOR NRF2, BRAIN IRON-METABOLISM, YA SUBUNIT GENE, OXIDATIVE STRESS, PARKINSONS-DISEASE, MITOCHONDRIAL DYSFUNCTION, MULTIPLE-SCLEROSIS, SIGNALING PATHWAY
  • Ankara Üniversitesi Adresli: Evet

Özet

Clinical and preclinical research indicates that neurodegenerative diseases are characterized by excess levels of oxidative stress (OS) biomarkers and by lower levels of antioxidant protection in the brain and peripheral tissues. Dysregulations in the oxidant/antioxidant balance are known to be a major factor in the pathogenesis of neurodegenerative diseases and involve mitochondrial dysfunction, protein misfolding, and neuroinflammation, all events that lead to the proteostatic collapse of neuronal cells and their loss. Nuclear factor-E2-related factor 2 (Nrf2) is a short-lived protein that works as a transcription factor and is related to the expression of many cytoprotective genes involved in xenobiotic metabolism and antioxidant responses. A major emerging function of Nrf2 from studies over the past decade is its role in resistance to OS. Nrf2 is a key regulator of OS defense and research supports a protective and defending role of Nrf2 against neurodegenerative conditions. This review describes the influence of Nrf2 on OS and in what way Nrf2 regulates antioxidant defense for neurodegenerative conditions. Furthermore, we evaluate recent research and evidence for a beneficial and potential role of specific Nrf2 activator compounds as therapeutic agents.