Circadian Regulation of Lipid Peroxidation in the Brain: Linking Ferroptosis to Neurodegenerative Vulnerability

Year : 2026 | Volume : 03 | Issue : 02 | Page : 1 14
    By

    Suraj Sen,

  • Anit Jha,

  • Rajeev Ratan,

  • Neeraj Yadav,

  • Ayush Bhardwaj,

  1. Principal, Dept. of Pharmacy, Harishchandra Pharmacy College, Jaunpur , U.P., India
  2. Academic Head, Dept. of Pharmacy, Harishchandra Pharmacy College, Jaunpur , U.P., India
  3. Assistant Professor, Dept. of Pharmacy, Harishchandra Pharmacy College, Jaunpur , U.P., India
  4. Scholar, Dept. of Pharmacy, Harishchandra Pharmacy College, Jaunpur , U.P., India
  5. Scholar, Dept. of Pharmacy, Harishchandra Pharmacy College, Jaunpur , U.P., India

Abstract

The human brain operates through highly coordinated physiological and biochemical processes that regulate cognition, behavior, and neural adaptability. Central to these processes are mechanisms governing brain function, neurophysiology, and neuroplasticity, which are increasingly recognized to be influenced by circadian rhythms. Recent advances in cognitive neuroscience, neuroimaging, and behavioral neuroscience have revealed that disruptions in circadian regulation can significantly impact oxidative balance within the brain, particularly through enhanced lipid peroxidation. Lipid peroxidation, a process involving oxidative degradation of membrane lipids, plays a crucial role in neuronal dysfunction and is closely associated with ferroptosis, an iron-dependent form of regulated cell death. The integration of neuropharmacology and drug development strategies has highlighted ferroptosis as a key therapeutic target in neurodegenerative conditions. Moreover, clinical neuropsychology studies indicate that oxidative damage and circadian misalignment contribute to cognitive decline and behavioral impairments. Neuroimaging and neurophysiological assessments further demonstrate that circadian disruption affects neuronal signaling, synaptic plasticity, and brain metabolism. Developmental neuroscience also suggests that early-life circadian disturbances may predispose individuals to long-term neurological vulnerabilities. The role of neuroplasticity in adapting to oxidative stress underscores the importance of maintaining circadian integrity for optimal brain health. This review explores the intersection of circadian rhythms, lipid peroxidation, and ferroptosis within the broader framework of neuroscience disciplines. It emphasizes how integrating concepts from cognitive, behavioral, and clinical neuroscience with pharmacological innovations can provide novel insights into neurodegenerative disease mechanisms. Additionally, it highlights emerging therapeutic approaches, including chronopharmacology and targeted antioxidant strategies, aimed at preserving neuronal function and improving clinical outcomes.

Keywords: Brain Function; Cognitive Neuroscience; Behavioral Neuroscience; Neuroimaging; Neurophysiology; Neuropsychology; Clinical Neuropsychology; Neuropharmacology; Drug Development; Developmental Neuroscience; Neuroplasticity; Circadian Rhythm; Lipid Peroxidation; Ferroptosis; Oxidative Stress

[This article belongs to International Journal of Brain Sciences ]

How to cite this article:
Suraj Sen, Anit Jha, Rajeev Ratan, Neeraj Yadav, Ayush Bhardwaj. Circadian Regulation of Lipid Peroxidation in the Brain: Linking Ferroptosis to Neurodegenerative Vulnerability. International Journal of Brain Sciences. 2026; 03(02):1-14.
How to cite this URL:
Suraj Sen, Anit Jha, Rajeev Ratan, Neeraj Yadav, Ayush Bhardwaj. Circadian Regulation of Lipid Peroxidation in the Brain: Linking Ferroptosis to Neurodegenerative Vulnerability. International Journal of Brain Sciences. 2026; 03(02):1-14. Available from: https://journals.stmjournals.com/ijbs/article=2026/view=244473


References

1. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley
AM, Yang WS, Morrison B. Ferroptosis: an iron-dependent form of nonapoptotic cell death. cell. 2012 May
25;149(5):1060-72.
2. Stockwell BR, Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE,
Noel K. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. cell. 2017
Oct 5;171(2):273-85.
3. Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nature reviews
Molecular cell biology. 2021 Apr;22(4):266-82.
4. Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation. Trends in cell biology. 2016 Mar
1;26(3):165-76.
5. Ursini F, Maiorino M, Forman HJ. Redox homeostasis: The Golden Mean of healthy living. Redox biology.
2016 Aug 1;8:205-15.
6. Brigelius-Flohé R, Maiorino M. Glutathione peroxidases. Biochimica et Biophysica Acta (BBA)-General
Subjects. 2013 May 1;1830(5):3289-303.
7. Hardeland R. Melatonin in aging and disease—multiple consequences of reduced secretion, options and
limits of treatment. Aging and disease. 2011 Feb 10;3(2):194.
8. Musiek ES, Holtzman DM. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science.
2016 Nov 25;354(6315):1004-8.
9. Hood S, Amir S. The aging clock: circadian rhythms and later life. The Journal of clinical investigation. 2017
Feb 1;127(2):437-46.
10. Kondratova AA, Kondratov RV. The circadian clock and pathology of the ageing brain. Nature Reviews
Neuroscience. 2012 May;13(5):325-35.
11. Zhang Y, Chen X, Gueydan C, Han J. Plasma membrane changes during programmed cell deaths. Cell
research. 2018 Jan;28(1):9-21.
12. Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M,
Walch A, Eggenhofer E, Basavarajappa D. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal
failure in mice. Nature cell biology. 2014 Dec;16(12):1180-91.
13. Do Van B, Gouel F, Jonneaux A, Timmerman K, Gelé P, Pétrault M, Bastide M, Laloux C, Moreau C, Bordet
R, Devos D. Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by
PKC. Neurobiology of disease. 2016 Oct 1;94:169-78.
14. Hambright WS, Fonseca RS, Chen L, Na R, Ran Q. Ablation of ferroptosis regulator glutathione peroxidase 4
in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox biology. 2017 Aug 1;12:8-
17.
15. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of
malondialdehyde and 4‐hydroxy‐2‐nonenal. Oxidative medicine and cellular longevity. 2014;2014(1):360438.

16. Butterfield DA, Halliwell B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nature
Reviews Neuroscience. 2019 Mar;20(3):148-60.
17. Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L. The role of iron in brain ageing and neurodegenerative
disorders. The Lancet Neurology. 2014 Oct 1;13(10):1045-60.
18. J. Reiter R, Tan DX, Rosales-Corral S, C. Manchester L. The universal nature, unequal distribution and
antioxidant functions of melatonin and its derivatives. Mini reviews in medicinal chemistry. 2013 Mar
1;13(3):373-84.
19. Terman M, Terman JS. Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and
side effects. CNS spectrums. 2005 Aug;10(8):647-63.
20. Cermakian N, Boivin DB. The regulation of central and peripheral circadian clocks in humans. Obesity
Reviews. 2009 Nov;10:25-36.
21. Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, Sun B, Wang G. Ferroptosis: past, present and future. Cell
death & disease. 2020 Feb 3;11(2):88.
22. Doll S, Conrad M. Iron and ferroptosis: a still ill‐defined liaison. IUBMB life. 2017 Jun;69(6):423-34.

Regular Issue Subscription Review Article
Volume 03
Issue 02
Received 05/05/2026
Accepted 12/05/2026
Published 20/05/2026
Publication Time 15 Days
35

Login


My IP

PlumX Metrics