Yetişkin fare beyninde ve periferik organlarda alfa-sinüklein hücre tipine özgü ifadenin topografik atlası

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neuron loss. Lewy pathology contains aggregated ⍺Synuclein (⍺Syn), a protein encoded by the SNCA gene which is also mutated or duplicated in a subset of familial PD cases. Due to its predominant presynaptic localization, immunostaining for the protein results in diffuse parenchymal reactivity, providing little insight into the types of cells expressing ⍺Syn. As a result, insight into ⍺Syn expression driven cellular vulnerability has been difficult to ascertain. Using a combination of knock-in mice that target ⍺Syn to the nucleus of cells (SncaNLS) and in situ hybridization of Snca in wild-type mice, we systematically mapped the topography and cell types expressing ⍺Syn in the mouse brain, spinal cord, retina, and gut. We find a high degree of correlation between ⍺Syn protein and RNA levels across multiple brain regions and further identify cell types with low and high ⍺Syn content. As expected, we found that ⍺Syn is highly expressed in neurons, particularly those involved in PD and to a lower extent in non-neuronal cell types, notably those of oligodendrocyte lineage, which are relevant to the pathogenesis of multiple system atrophy. Surprisingly, we also find that ⍺Syn is relatively absent from select neuronal clusters, e.g., ChAT-positive motor neurons, whereas enteric neurons universally express some degree of ⍺Syn. We also present a web-based platform allowing for user-friendly interrogation of these results. Taken together, this integrated atlas provides much-needed insight into the cellular topography of ⍺Syn, and provides a quantitative map to test hypotheses about the role of ⍺Syn in network vulnerability, and thus serves investigations into PD pathogenesis and other αSynucleinopathies.

İlgili konular