The role of abnormal alpha-synuclein and its partners in synucleinopathy

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Abnormal synuclein is deposited in the presynapses and cytoplasmic inclusions found in synucleinopathy such as Parkinsons disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Likewise, NUB1 is also accumulated in these specific regions together with abnormal synuclein. Although NUB1 can degrade synuclein expressed in cultured cells, it is not clear that NUB1 possesses this ability in vivo. We created transgenic mice expressing NUB1 and synuclein to investigate the role of NUB1 on abnormal synuclein deposition. Immunohistochemical and biochemical studies confirmed that NUB1 was expressed in the neurons. Unexpectedly, however, there were no alterations of abnormal synuclein deposition between mice expressing synuclein and synuclein/NUB1. These results suggest that NUB1 unlikely degrades synuclein in vivo.