Genetic suppressions of CRMP2 phosphorylation ameliorate α-synuclein accumulation in an α-synucleinopathy mouse model.

α-synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of phosphorylated α-synuclein, forming the primary component of Lewy bodies. Current treatments can alleviate symptoms, however, there is still a lack of understanding in the mechanisms involved in the pathological processes, making difficult the development of novel therapies that can hinder the neurodegeneration. Phosphorylation of CRMP2 has previously been reported to contribute to the synaptic deficits observed in these disorders. Moreover, prior research has found increased phosphorylation of CRMP2 in DLB patients, hinting a possible involvement of CRMP2 in the pathological processes of these diseases. Therefore, in this study we used an A53T mouse model in which CRMP2 phosphorylation is prevented (A53T;CRMP2KI mice) to evaluate changes in α-synuclein accumulation and neuroinflammation. As a result, we were able to observe a reduction in phosphorylated α-synuclein (pα-synuclein) accumulation in the CA1 region of the hippocampus along with a reduction in microglia number. In addition, we were able to observe an improvement in the cognitive impairment that these mice tend to present. Taken together, these findings reaffirm the role of CRMP2 in α-synucleinopathies and suggest that CRMP2 might be a potential therapeutic target for these neurodegenerative diseases.