Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (9): 4020-4027.doi: 10.4103/NRR.NRR-D-25-00233

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 Long non-coding RNAs: Emerging regulators of diverse programmed cell death pathways in neurons

Noah C. Mathew1, Kevin K. Park1, 2, 3, *   

  1. 1Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 
    2Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; 
    3Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
  • Online:2026-09-15 Published:2026-05-16
  • Contact: Kevin K. Park, PhD, kyung.park@utsouthwestern.edu.
  • Supported by:
    This work was supported by grants from the National Eye Institute (NEI) R01EY032542, P30EY030413, and Challenge Grant from Research to Prevent Blindness (all to KKP).

Abstract: Long non-coding RNAs have emerged as pivotal regulators of diverse biological processes, particularly in the modulation of regulated neuronal cell death pathways. This review highlights the roles of long non-coding RNAs in programmed neuronal cell death, focusing on apoptosis, necroptosis, ferroptosis, and pyroptosis. Dysregulation of these processes contributes to neurodegenerative disorders and neurological injuries, emphasizing the importance of understanding how long non-coding RNAs influence these pathways. Apoptosis, essential for neuronal development, can lead to pathology when misregulated. Necroptosis, a caspase-independent inflammatory process, involves the modulation of necrosome components. Pyroptosis, mediated by inflammasomes, affects inflammasome assembly and cytokine release. Ferroptosis, driven by iron accumulation and lipid peroxidation, is influenced by changes in antioxidant defenses. By detailing the roles of long non-coding RNAs in these mechanisms, this review underscores their therapeutic potential for mitigating neuronal loss.

Key words: apoptosis, lncRNA, necroptosis, neuronal death, non-coding RNA