Poli (ADP-riboz) polimeraz 1 inhibisyonu nörodejenerasyonu önler ve transkripsiyon faktörü EB-bağımlı otofaji yoluyla Parkinson hastalığının ⁇ -sinükleinA53T modelinde ⁇ -sinüklein bozulmasını teşvik eder.

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Poly (ADP-ribose) polymerase 1 (PARP1) is a master regulator of diverse biological processes such as DNA repair, oxidative stress, and apoptosis. PARP1 can be activated by aggregated α-synuclein, and this process in turn exacerbates toxicity of α-synuclein. This circle is closely linked to the evolution of Parkinson's disease (PD) that characterized by progressive neurodegeneration and motor deficits. Here, we reported the PARP1, as a novel upstream molecular of transcription factor EB (TFEB), participates in regulation of autophagy in α-synuclein aggregated cells and mice. PARP1 inhibition not only enhances the nuclear transcription of TFEB via SIRT1 mediated down-regulation of mTOR signaling but also reduces nuclear export of TFEB by attenuating the TFEB-CRM1 interaction. Our results revealed that PARP1 inhibition lessened the accumulation of α-synuclein in PD models. Also, oral administration of PARP1 inhibitor Veliparib prevented neurodegeneration and improved motor ability in α-synucleinA53T transgenic mice. These findings identify that PARP1 signaling pathway regulates TFEB-mediated autophagy, pointing to potential therapeutic strategy of PD via enhancing protein degradation systems.

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