INTERNATIONAL ASSOCIATION OF BIOMEDICAL SCIENCES

  “ IABS Forum-2023 ” December 2023
ABSTRACT

Elovanoids are Neural Resiliency Epigenomic Regulators Targeting Histone Modifications, DNA Methylation, Tau Phosphorylation, Telomere Integrity, Senescence Programming, and Dendrite Integrity

Surjyadipta Bhattacharjee, Pranab K. Mukherjee, and Nicolas G. Bazan

Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112, USA

  ABSTRACT

 Cellular identity, developmental reorganization, genomic structure modulation, and susceptibility to neurodegenerative diseases involve epigenomic regulation engaging multiple signaling interplay. Here we demonstrate that elovanoids (ELVs), mediators derived from very-long-chain polyunsaturated fatty acids (VLC-PUFAs, n-3, C >28), and their precursors in human neurons/astrocytes in culture overcome the damage triggered by oligomeric amyloid-β (OAβ), erastin (ferroptosis-dependent cell death), or other insults like uncompensated oxidative stress (UOS), NMDA mediated cellular excitotoxicity, or oxygen-glucose deprivation (OGD), that target epigenomic signaling. We uncover that ELVs counteract damage targeting histones H3K9 and H3K27 methylation and acetylation; tau hyperphosphorylation (pThr181, pThr217, pThr231, and pSer202/pThr205 (AT8)); senescence gene programming (p16INK4a, p27KIP, p21CIP1, and p53); and DNA methylation (DNAm) modifying enzymes: TET (DNA hydroxymethylase), DNA methyltransferase, DNA demethylase, and DNA methylation (5mC) phenotype. Moreover, ELVs revert OAβ-triggered telomere length (TL) attrition as well as upregulation of telomerase reverse transcriptase (TERT) expression fostering dendrite protection and neuronal survival. Thus, ELVs modulate epigenomic resiliency by pleiotropic interrelated signaling.

 ACKNOWLEDGMENTS

   Research support from the National Institute of Neurological Disorders and Stroke grants R01NS104117 (NGB) and R01NS109221 (NGB) and the National Eye Institute grant R01EY005121 (NGB), NIH.

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