Linking acetylated α-Tubulin redistribution to α-Synuclein pathology in brain of Parkinson’s disease patients

Linking acetylated α-Tubulin redistribution to α-Synuclein pathology in brain of Parkinson’s disease patients

2024 | Samanta Mazzetti, Federica Giampietro, Alessandra Maria Calogero, Huseyin Berkcan Isilgan, Gloria Gagliardi, Chiara Rolando, Francesca Cantele, Miriam Ascagni, Manuela Bramero, Giorgio Giaccone, Ioannis Ugo Isaias, Gianni Pezzoli, Graziella Cappelletti
This study investigates the role of acetylated α-tubulin redistribution in Parkinson's disease (PD) pathology, focusing on its relationship with α-synuclein aggregation and Lewy body (LB) formation. Using post-mortem human brain samples from PD patients and controls, the researchers observed a redistribution of acetylated α-tubulin in subcortical regions, particularly in neuronal cell bodies, while its levels decreased in axonal compartments. This redistribution was linked to α-synuclein oligomerization and phosphorylated Ser129 α-synuclein, suggesting a potential role in LB formation. The study also identified threadlike structures resembling tunnelling nanotubes containing α-synuclein oligomers and associated with acetylated α-tubulin-enriched neurons. These findings support the hypothesis that acetylated α-tubulin plays a significant role in PD pathogenesis and LB formation. The study highlights the complex interplay between acetylated α-tubulin and α-synuclein, providing insights into the mechanisms underlying PD progression. The results suggest that acetylated α-tubulin may be involved in the early stages of α-synuclein aggregation and the formation of LBs, and that its redistribution could be a key factor in the disease's progression. The study also underscores the importance of in vivo analysis in understanding the complex pathological processes of PD.This study investigates the role of acetylated α-tubulin redistribution in Parkinson's disease (PD) pathology, focusing on its relationship with α-synuclein aggregation and Lewy body (LB) formation. Using post-mortem human brain samples from PD patients and controls, the researchers observed a redistribution of acetylated α-tubulin in subcortical regions, particularly in neuronal cell bodies, while its levels decreased in axonal compartments. This redistribution was linked to α-synuclein oligomerization and phosphorylated Ser129 α-synuclein, suggesting a potential role in LB formation. The study also identified threadlike structures resembling tunnelling nanotubes containing α-synuclein oligomers and associated with acetylated α-tubulin-enriched neurons. These findings support the hypothesis that acetylated α-tubulin plays a significant role in PD pathogenesis and LB formation. The study highlights the complex interplay between acetylated α-tubulin and α-synuclein, providing insights into the mechanisms underlying PD progression. The results suggest that acetylated α-tubulin may be involved in the early stages of α-synuclein aggregation and the formation of LBs, and that its redistribution could be a key factor in the disease's progression. The study also underscores the importance of in vivo analysis in understanding the complex pathological processes of PD.
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