AI Article Synopsis
- The study explores the role of alpha synuclein (aSyn) in Parkinson's disease (PD), particularly its aggregation and how it affects neurodegeneration.
- Researchers identified a new antibody (Nu-aSyn-C) that specifically targets nuclear aSyn, revealing that nuclear aSyn has different structural properties compared to cytosolic aSyn, showing increased phosphorylation and assembly in proliferating cells.
- The research also indicates that as neurons differentiate, aSyn redistributes from the nucleus to the soma and then to neuronal processes, with this distribution pattern being disrupted in neurons from PD patients with aSyn gene duplication.
Article Abstract
Alpha synuclein (aSyn) and its aggregation are crucial for the neurodegeneration of Parkinson's disease (PD). aSyn was initially described in the nucleus and presynaptic nerve terminals. However, the biology of nuclear aSyn and the link of aSyn between subcellular compartments are less understood. Current knowledge suggests the existence of various aSyn species with distinct structural and biochemical properties. Here, we identified a C-terminal-targeting aSyn antibody (Nu-aSyn-C), which has a high immunoaffinity towards aSyn in the nucleus. Comparing the Nu-aSyn-C antibody to aSyn antibodies developed against phosphorylated or aggregated forms, we observed that nuclear aSyn differs from cytosolic aSyn by an increased phosphorylation and assembly level in proliferating cells. Employing Nu-aSyn-C, we characterized aSyn distribution during neuronal differentiation in midbrain dopaminergic neurons (mDANs) derived from human-induced pluripotent stem cells (hiPSCs) and Lund human mesencephalic cells, and in primary rat hippocampal neurons. We detected a specific translocation pattern of aSyn during neuronal differentiation from the nucleus to the soma and finally to neuronal processes. Interestingly, a remarkable shift of Nu-aSyn-C-positive species towards neurites was detected in hiPSC mDANs from a PD patient carrying aSyn gene duplication. Together, our results reveal distinct nuclear and cytosolic aSyn species that redistribute during neuronal differentiation-a process that is altered in PD-derived neurons.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406079 | PMC |
| http://dx.doi.org/10.3390/biom12081108 | DOI Listing |
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