Astrocytic cathepsin D promotes α-synuclein processing and Lewy neurite-like aggregate maturation.

Astrocytic cathepsin D facilitates α-synuclein processing and promotes Lewy neurite-like aggregate maturation in a neuron-astrocyte co-culture system.

• Why it matters: Understanding how astrocytes contribute to α-synuclein pathology is crucial because their active role in aggregate processing and transfer may influence Parkinson's disease progression and propagation mechanisms.
• What they did: The study used a physiologically relevant neuron-astrocyte co-culture system to show that astrocytes internalize α-syn pre-formed fibrils, generate C-terminally truncated α-syn via Cathepsin D, and transfer α-syn material to neurons, promoting aggregate maturation.
• The result: Findings suggest that lysosomal remodeling in astrocytes, involving Cathepsin D, contributes to the morphological maturation and intercellular spread of α-synuclein pathology, highlighting astrocytes' active role in disease propagation.