Unraveling the Neuroprotective Role of NATO3 in Dopaminergic Neurons

Diplôme Thèse Unraveling the Neuroprotective Role of NATO3 in Dopaminergic Neurons eng 2024 2024 author Valencia Alarcon Eva Paulina 931836 director Nagoshi Emi 0000-0002-6365-4074 535940 Département de génétique et évolution (Genev) (BIANI) 10.13097/archive-ouverte/unige:176765 urn:nbn:ch:unige-1767654 Sc. Vie 273 Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta, leading to various motor and non-motor disabilities. Its high prevalence and significant impact on quality of life underscore the urgent need for innovative treatments. This study investigated the post-developmental role of Nato3, a crucial transcription factor for midbrain DA neurogenesis, using a mouse model with conditional Nato3 ablation (Nato3 cKO) in differentiated DA neurons. Employing immunohistochemistry, electron microscopy, RNA-sequencing, and behavioral assays, we found that Nato3 cKO mice recapitulate PD-like symptoms, including progressive locomotor decline, loss of mitochondrial integrity, and autophagy defects. Furthermore, human NATO3 overexpression ameliorated cellular phenotypes associated with PD pathology, suggesting NATO3's involvement in autophagy-lysosomal system dynamics and mitochondrial health. These findings provide insights into NATO3's role in PD pathology and potential therapeutic targets. Dewey 590 44 Département de génétique et évolution 162 false 826 Groupe Nagoshi 744e5b59-fde3-4fc1-9d96-b25deb8ddc42 Thesis Restricted THESIS_EVA_VALENCIA_ALARCON_IMPRIMA.pdf 42986453 application/pdf Private 2026-03-11 40c1738e61671b2354b4d4b7cfff830dbbe607ce1e2e4b7da117053762239c0d 88d15648-f772-43eb-972c-f224bcb3e6fc Imprimatur Public Imprimatur_Thesis_ValenciaAlarcon.pdf 181312 application/pdf ea02dcbaee04f77e40472997b4f8a90c3641016e7160c8a2595c007fd1ffb99d restrictedAccess Faculté des sciences / Section de biologie / Département de génétique et évolution

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Unraveling the Neuroprotective Role of NATO3 in Dopaminergic Neurons				2024	307	1

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Valencia Alarcon, Eva Paulina

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