Impact of Sleep Deprivation on Major Neuroinflammatory Signal Transduction Pathways

Arehally M. Mahalakshmi*, Prithvi Lokesh, Tousif Ahmed Hediyal, Manjunath Kalyan, Chandrasekaran Vichitra, Musthafa Mohamed Essa, M. Walid Qoronfleh, Seithikurippu R. Pandi-Perumal, Saravana Babu Chidambaram

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Sleep deprivation (SD) is emulating an epidemic imparting detrimental effects ranging from immediate repercussions like vehicle accidents to very serious neurological disorders. All age groups are vulnerable to SD either because of lifestyle or illness. This imposes a significant burden on public health and safety. SD triggers an array of inflammatory responses, and neuroinflammation is one of the most common complications. Changes in circulation levels of pro- and anti-inflammatory cytokines caused by SD are associated with higher and lower levels of inflammation, respectively. SD-induced astrogliosis, microgliosis, impaired glymphatic clearance, BBB disruption, and release of inflammatory cytokines are the main sources of neuroinflammation. This review addresses the clinical and experimental SD and the associated activation of neuroinflammatory signaling via NF-κB, TNF-α, CREB, TLR, Nrf2, JAK-STAT, MAPK, and mTOR proteins. Major neurodegenerative disorders (e.g., Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS) all have these signaling molecules as crucial participants in their etiology. Hence, SD has a strong association with the initiation and progression of neurodegenerative diseases. Further research in this area is warranted to understand the role of the activated neuroinflammatory pathways in the initiation, progression, and manifestations of neurological disorders.

Original languageEnglish
Pages (from-to)101-114
Number of pages14
JournalSleep and Vigilance
Issue number1
Publication statusPublished - Jun 2022


  • Neurodegenerative disease
  • Neuroinflammation
  • Oxidative stress
  • Signaling pathways
  • Sleep deprivation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

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