Screening for Neurotoxicity

Human iPSC → neural progenitor cells → differentiated neurons → compound exposure → multiparametric neurotoxicity assessment

Domain

Assay

Example biomarkers/readouts

Cell viability

ATP/CellTiter-Glo

ATP reduction

Cytotoxicity

LDH release

Membrane damage

Apoptosis

Caspase-3/7

Apoptotic signaling

Neuronal identity

MAP2, NeuN, βIII-tubulin

Neuronal integrity

Neurite toxicity

High-content imaging

Neurite length/branching

Synaptic toxicity

Synapsin-1, PSD95

Synaptic density

Mitochondrial toxicity

TMRE/TMRM, MitoTracker

ΔΨm and mitochondrial mass

Oxidative stress

ROS assays

ROS accumulation

Calcium homeostasis

Ca²⁺ imaging

Abnormal Ca²⁺ activity

Electrophysiology

MEA/patch clamp

Firing rate/network activity

Neuroinflammation

IL-6, TNF-α, MCP-1

Inflammatory response

Axonal injury

NF-H, SMI-32

Axonal damage

Cellular stress

ATF4, CHOP, HSP70

ER/proteotoxic stress