Lysosomal stress drives the release of pathogenic α-synuclein from macrophage lineage cells via the LRRK2-Rab10 pathway

Abe, Tetsuro; Kuwahara, Tomoki; Suenaga, Shoichi; Sakurai, Maria; Takatori, Sho; Iwatsubo, Takeshi

doi:10.1016/j.isci.2024.108893

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2024

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Cited by 4 publications

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Alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions

Bayati,

McPherson

2024

Journal of Biological Chemistry

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Alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions

Bayati,

McPherson

2024

Journal of Biological Chemistry

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Low-dose radiation decreases Lrrk2 levels in the striatum of large mammalian brains: New venues to treat Parkinson's disease?

Iacono,

Murphy,

Stimpson

et al. 2024

Parkinsonism & Related Disorders

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Antitumoral potency of isorhamnetin and its derivates carbohydrate in methanol extract from Nitraria retusa leaves

Boubaker,

Lahmar,

Toumia

et al. 2024

Preprint

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Background Nitraria retusa is a traditional Tunisian herb that has been widely used in folk medicine for its great remedies. In this study, we evaluated the antitumoral potency of methanol extract from leaves of Nitraria retusa, (Nr-MeOH) via its major compounds isorhamnetin and its carbohydrate derivatives against human lymphoblastoid cells (TK6), breast cancer murine cells (4T1), and in tumor-bearing mice. Methods The Nr-MeOH was analysed by LC-MSn to determine the major compounds. The cell apoptotic mechanism was described using DNA fragmentation and double staining annexin/propidium iodide by flow cytometry. The PARP cleavage was investigated by Western blotting. BALB/c mice were subcutaneously inoculated with 4T1 cells, and then treated intra-peritoneally with the methanol extract for 21 days. The tumor growth was evaluated. Macrophage phagocytosis was assessed by measuring the lysosomal activity and the nitric oxide production. Results Our investigation showed that the Nr-MeOH contains various flavonoids, quercetin, isorhamnetin 3-O-glucoside, isorhamnetin-3-O-rutinoside, isorhamnetin glucuronide, and isorhamnetin. These compounds were found to induce apoptosis in the cancer cell line tested and to reduce tumor growth rates in induced 4T1-bearing tumor mice. Conclusion The results of this work suggest that Nitraria retusa could be a substitute for wild resource as an anticancer therapy.

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Lysosomal stress drives the release of pathogenic α-synuclein from macrophage lineage cells via the LRRK2-Rab10 pathway

Cited by 4 publications

References 60 publications

Alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions

Alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions

Low-dose radiation decreases Lrrk2 levels in the striatum of large mammalian brains: New venues to treat Parkinson's disease?

Antitumoral potency of isorhamnetin and its derivates carbohydrate in methanol extract from Nitraria retusa leaves

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