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Subcellular localization

Ciliary associated gene, Nucleoplasm, Cytosol

Functional category

• Signaling (Hedgehog
• GPCRs
• ion channels)
• Ciliary assembly/disassembly

Function

We performed an unbiased transcriptomic analysis of cortical neurons isolated from patients with PD to identify dysregulated pathways and determine their potential contributions to the disease process. We discovered that genes associated with primary cilia, non-synaptic sensory and signaling organelles, are upregulated in both early and late stage PD patients. Enhancing ciliogenesis in primary cortical neurons via sonic hedgehog signaling suppressed the accumulation of α-synuclein pathology in vitro. Interestingly, deletion of Tet2 in mice also enhanced the expression of primary cilia and sonic hedgehog signaling genes and reduced the accumulation of α-synuclein pathology and dopamine neuron degeneration in vivo. Our findings demonstrate the crucial role of TET2 loss in regulating ciliogenesis and potentially affecting the progression of PD pathology(40189544).