A Proteomics Profiling Reveals the Neuroprotective Effects of Melatonin on Exogenous β-amyloid-42 Induced Mitochondrial Impairment, Intracellular β-amyloid Accumulation and Tau Hyperphosphorylation in Human SH-SY5Y Cells.
Level 5 - mechanism / opinion, no new human data
In vitro bench study using an immortalized human cell line (SH-SY5Y).
PubMed 40047119 · doi:10.1002/cbin.70013
What was done
Human neuroblastoma SH-SY5Y cells were exposed to exogenous beta-amyloid-42 (Aβ42) with or without melatonin pretreatment. Alterations in protein expression were evaluated using label-free nano-LC-MS/MS proteomics. Findings were experimentally validated using Milliplex magnetic bead assays for Aβ and tau, Western blot analysis, and measurements of reactive oxygen species (ROS) generation and mitochondrial membrane potential.
What was found
Aβ42 exposure elevated intracellular Aβ42/40 and phosphorylated tau (Thr181)/total tau ratios in SH-SY5Y cells. Melatonin pretreatment reduced these pathogenic protein levels. Proteomics revealed shifts in proteins involved in Alzheimer's disease pathways, synaptic function, apoptosis, the mitochondrial permeability transition pore, electron transport chain, and oxidative stress. Melatonin suppressed mitochondrial ROS generation and attenuated mitochondrial membrane depolarization. The abstract reports no quantitative values or effect sizes.
Why it matters
This study maps proteomic alterations involved in Aβ42 toxicity and demonstrates how melatonin modulates mitochondrial and apoptotic pathways in a cellular model of Alzheimer's pathology.
Limits
Findings are limited to an in vitro immortalized cell line (SH-SY5Y), lacking in vivo validation in animal models or human subjects. The abstract does not report sample sizes, replication counts, concentrations used, or numerical effect estimates.
Cited by
- supports Beta-amyloid triggers both the pathological phosphorylation of tau protein and the production of reactive oxygen species in the brain.