The Brown Algal Phlorotannin Dieckol Attenuates Amyloid-β Oligomer-Induced Oxidative DNA Damage and Senescence-like Stress in Human Neuron-like Cells.

Amyloid-β oligomers (AβOs) induce oxidative and genomic stress that may promote neuronal senescence-like alterations in Alzheimer's disease. Dieckol, a brown algal phlorotannin, has antioxidant and neuroprotective properties, but its effects on AβO-induced senescence-like stress remain unclear. Differentiated SH-SY5Y cells were pretreated with dieckol (10-50 μmol/L) or the receptor for advanced glycation end products (RAGE) antagonist azeliragon (100 μmol/L) for 24 h, followed by AβO (20 μmol/L) exposure for 24 h. Dieckol concentration-dependently preserved cell viability, as indirectly assessed by the MTT assay and reduced mitochondrial superoxide accumulation. Dieckol also decreased senescence-associated β-galactosidase positivity, H3K9me2/3-associated chromatin remodeling, and interleukin-1β, interleukin-6, and tumor necrosis factor-α secretion while partially restoring telomerase activity. This restoration was consistent with improved cellular stress resilience in the differentiated neuron-like model. Furthermore, dieckol reduced 8-hydroxy-2'-deoxyguanosine and γ-H2AX accumulation and attenuated ATM-Chk2-p53 DNA damage response signaling. Azeliragon elicited broadly similar responses; however, these similarities do not establish RAGE dependence or a shared mechanism of action. Collectively, dieckol concurrently attenuated mitochondrial oxidative stress, DNA damage response signaling, and senescence-associated alterations. Although these parallel effects support a possible relationship among these processes, their causal and temporal relationships remain to be established.