Research ReportNeurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson's disease

- Neurogranin gene expression is increased in a mouse model of synucleinopathies.
- α-Synuclein colocalizes with neurogranin occurs in a mouse model of synucleinopathies.
- Neurogranin is bound to α-synuclein in the human brain.
- Neurogranin bound to α-synuclein is decreased in Parkinson's disease.
- Phosphorylated neurogranin is decreased in Parkinson's disease and dementia with Lewy bodies.

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson's disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson's disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson's disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson's disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory.