TGFb signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration - PubMed
3 hours ago
- #Astroglial Activation
- #Neurodegeneration
- #TDP-43 Proteinopathy
- Dominant GRN mutations cause frontotemporal lobar degeneration (FTLD-GRN), while homozygous mutations lead to neuronal ceroid lipofuscinosis.
- Using iPSC-derived cortical organoids, GRN mutations caused precocious astrogliosis, leading to neuronal stress and synaptic loss.
- Single-cell analyses showed activated TGFb signaling in astrocytes, with immune activation, loss of synaptic support, and cytoplasmic pTDP-43 fibrils.
- Blocking TGFb signaling reduced astroglial activation and pTDP-43 proteinopathy in GRN-/- organoids, highlighting astroglia's role in neurodegeneration.