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Advanced Cellular Models for Neurodegenerative Diseases and PFAS-Related Environmental Risks.

Davide Rotondo1, Laura Lagostena2, Valeria Magnelli1

  • 1Department of Science and Technological Innovation, Università del Piemonte Orientale, 15121 Alessandria, Italy.

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Summary
This summary is machine-generated.

Advanced cell models reveal how per- and polyfluoroalkyl substances (PFAS) cause neurotoxicity. These systems help understand PFAS impacts on brain diseases and develop risk assessments.

Keywords:
gene–environment interactionsinduced pluripotent stem cells (iPSC)microphysiological systemsneurotoxicityper- and polyfluoroalkyl substances (PFAS)

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Area of Science:

  • Neuroscience
  • Toxicology
  • Biomedical Engineering

Background:

  • Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants linked to neurotoxicity.
  • Understanding PFAS neurotoxicity mechanisms requires human-relevant models that assess exposure, barrier function, and brain circuitry.

Purpose of the Study:

  • To review advanced cellular platforms for modeling PFAS neurotoxicity relevant to Alzheimer's, Parkinson's, and multiple sclerosis.
  • To identify convergent PFAS-responsive biological processes and outline principles for exposure design and standardization.

Main Methods:

  • Utilized induced pluripotent stem cell (iPSC)-derived neuronal and glial cultures, organoids, and chip-based microphysiological systems.
  • Employed blood-brain barrier (BBB)-on-chip models coupled with brain organoids for controlled, chronic PFAS exposure.
  • Assessed barrier integrity (TEER), PFAS translocation, and downstream neuronal-glial responses via electrophysiology and multi-omics.

Main Results:

  • Advanced models successfully replicated disease-relevant phenotypes under controlled PFAS exposure.
  • Convergent PFAS-responsive pathways identified include mitochondrial dysfunction, oxidative stress, lipid dysregulation, neuroinflammation, and synaptic impairments.
  • These findings provide a mechanistic basis for biomarker discovery and gene-environment interaction studies.

Conclusions:

  • Advanced cellular platforms offer robust systems for evaluating PFAS neurotoxicity and its mechanisms.
  • These models facilitate the development of quantitative risk assessments and therapeutic strategies for PFAS-related neurological disorders.