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Updated: Jan 10, 2026
Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
Published on: August 16, 2020
Attenuating α-synuclein pathology in mice with in situ engineered astrocytes
Xiao-Yu Du1,2, Jing Zhou3, Jie Zhu1,2
1National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, 100190, China.
Background:
α-Synuclein oligomers (α-synOs) contribute to the initiation and progression of Parkinson's disease (PD) by promoting neuronal death and activating glial cells. Clearing α-synOs while maintaining tissue homeostasis is a promising therapeutic strategy for PD.
Methods:
We genetically engineered astrocytes with an anti-α-synO chimeric antigen receptor (CAR) consisting of a single-chain variable fragment targeting α-synOs and a truncated MerTK receptor, to direct their phagocytic activity against α-synOs.
Results:
CAR-engineered astrocytes (CAR-A) showed significantly enhanced phagocytosis of α-synOs due to effective activation of Rac1, Cdc42 and RhoA and markedly decreased the release of pro-inflammatory cytokines by inhibiting the NF-κB and cytokine receptor signaling pathways. Consistently, in situ CAR-A significantly ameliorated the motor and cognitive deficits of A53T mice by clearing α-synOs, creating a non-inflammatory microenvironment and restoring the viability of dopaminergic neurons.
Conclusions:
CAR-A-based strategy is an effective treatment for PD-like mouse model. This in situ CAR-A technology provides an innovative and feasible strategy to treat PD and other brain disorders.
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