Investigations on the effects of SH2B2 on Parkinson’s disease based on its in vivo and in vitro neurotoxic model
簡(jiǎn)介:
- 作者: Lihui Zhao, Ke Han, Lifeng Sun
- 雜志: Neuroscience
- Doi: https://www.doi.org/10.1016/j.neuroscience.2025.12.069
- 出版日期: 2026/3/5
摘要
Parkinson’s disease (PD) is characterized by dopaminergic neuron loss, motor dysfunction, and Lewy body formation. Src homology 2B adaptor protein 2 (SH2B2), a member of the SH2B family with known roles in neuroregulation, has not been fully explored in PD. This study aimed to investigate the neuroprotective effects and mechanisms of SH2B2 in PD. MPTP-induced mouse model and MPP+-treated SH-SY5Y cell model were established to simulate PD in vivo and in vitro. Mice were randomly divided into saline, MPTP, MPTP + OE-NC, and MPTP + OE-SH2B2 groups, while SH-SY5Y cells were randomly grouped into control, MPP+, MPP+ + OE-NC, and MPP+ + OE-SH2B2. Behavioral tests, Nissl staining, IHC, CCK-8, flow cytometry, qRT-PCR, and Western blot were used to assess outcomes. Our findings indicated that SH2B2 was downregulated in MPTP-induced mice and MPP+-treated SH-SY5Y cells (P < 0.01). Overexpressing SH2B2 improved motor function in mice (evidenced by the prolonged rotarod and wire hang latencies and shortened pole climbing time (P < 0.01)), upregulated TH expression (P < 0.001), downregulated IBA1 levels (P < 0.001), and alleviated dopaminergic neuron atrophy and Nissl body loss (P < 0.001). In SH-SY5Y cells, overexpressing SH2B2 reversed MPP+-induced cell viability reduction and apoptosis (P < 0.05). This study confirmed SH2B2 downregulation in PD models and demonstrated that overexpressing SH2B2 alleviates dopaminergic neuron injury and neuroinflammation, improving motor function. Therefore, SH2B2 emerges as a novel neuroprotective factor and potential therapeutic target for PD, warranting further research into its molecular mechanisms for clinical translation.
關(guān)于派真
作為一家專注于AAV 技術(shù)十余年,深耕基因治療領(lǐng)域的CRO&CDMO,派真生物可提供從載體設(shè)計(jì)、構(gòu)建到 AAV、慢病毒和 mRNA 服務(wù)的一站式解決方案。憑借深厚的技術(shù)實(shí)力、卓越的運(yùn)營(yíng)管理和高標(biāo)準(zhǔn)的服務(wù)交付,我們?yōu)槿蚩蛻籼峁┮徽臼?/span>CMC解決方案,包括從早期概念驗(yàn)證、成藥性評(píng)估到IIT、IND及BLA的各個(gè)階段。
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憑借我們獨(dú)立知識(shí)產(chǎn)權(quán)的π-alphaTM 293 細(xì)胞AAV高產(chǎn)技術(shù)平臺(tái),我們能將AAV產(chǎn)量提高多至10倍,每批次產(chǎn)量可達(dá)1×101?vg,以滿足多樣化的商業(yè)化和臨床項(xiàng)目需求。此外,我們定制化的mRNA和脂質(zhì)納米顆粒(LNP)產(chǎn)品及服務(wù)覆蓋藥物和疫苗開發(fā)的各個(gè)階段,從研發(fā)到符合GMP的生產(chǎn),提供端到端的一站式解決方案。