[IF 15.2] Absin Products Facilitate PD Mechanism Research: Novel Discovery of Mitochondrial Dysfunction Induced by Disrupted AMPK-SENP1-Sirt3 Signaling

Parkinson's disease (PD) is a progressive neurodegenerative disorder with complex and incompletely elucidated pathogenesis. A recent study published in Translational Neurodegeneration provides critical new insights into PD pathogenesis by revealing how disrupted AMPK-SENP1-Sirt3 signaling impairs mitochondrial complex I (CI) function in the MPTP-induced PD model.

I. Research Rationale: Layered Investigation Focusing on Signaling Pathway-Mitochondrial Function Interactions

(1) Defining the Core Scientific Question

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly employed to induce PD models, disrupting mitochondrial CI function and causing nigrostriatal dopaminergic neuronal loss. However, the specific molecular pathways through which MPTP damages mitochondrial CI function remain poorly characterized. Therefore, the research team aimed to identify the molecular mechanisms by which MPTP regulates CI function and determine the specific CI subunits affected by MPTP exposure.

(2) Designing In Vivo and In Vitro Validation Systems

• In Vivo Experiments: Wild-type Sirt3 and Sirt3 K223R desumoylation mutant male mice were utilized. PD models were established via intraperitoneal injection of MPTP or physiological saline, followed by assessment of motor performance, mitochondrial function, and protein acetylation levels.
• In Vitro Experiments: SH-SY5Y cell lines with or without Sirt3 desumoylation mutations were employed to simulate MPTP-induced environments for in-depth mechanistic investigation. This combined in vivo and in vitro experimental design enables comprehensive and accurate validation of the relevant signaling pathways.

(3) Focusing on Key Signaling Pathways and Molecular Modifications

The research team focused on the AMPK-SENP1-Sirt3 signaling cascade, with particular emphasis on how SUMOylation modifications affect Sirt3 deacetylase activity and subsequently influence mitochondrial CI subunit acetylation levels and CI function, progressively dissecting the molecular chain of MPTP-induced PD pathogenesis.

II. Research Findings: Disrupted AMPK-SENP1-Sirt3 Signaling as a Key PD Pathogenic Mechanism

(1) MPTP Disrupts the AMPK-SENP1-Sirt3 Axis, Triggering Mitochondrial Dysfunction

Both in vivo and in vitro experiments demonstrated that MPTP exposure inhibits AMPK activation and impedes SENP1 mitochondrial translocation. Deficiency of mitochondrial SENP1 leads to elevated Sirt3 SUMOylation levels, thereby suppressing its deacetylase activity. These sequential alterations result in significantly increased acetylation of CI subunits NDUFS3 and NDUFA5, ultimately causing reduced CI activity, mitochondrial dysfunction, and dopaminergic neuronal death.

(2) Sirt3 Desumoylation Mutation Alleviates MPTP-Induced Pathological Damage

Constitutive Sirt3 desumoylation mutations (K223R in mice, K288R in humans) attenuated MPTP-induced mitochondrial disturbances while reducing dopaminergic neuronal loss and ameliorating behavioral deficits. This finding provides a potential molecular target for PD therapeutics.

(3) Supporting Experimental Data

III. Absin Product Support: ELISA Kits for Precise Inflammatory Cytokine Detection

To evaluate neuroinflammatory responses in this study, the research team utilized Absin's IL-6 ELISA Kit (Catalog: abs520004) and TNF-α ELISA Kit (Catalog: abs520010) to detect levels of these inflammatory cytokines in cell culture supernatants.

(1) Product Application Scenarios

Researchers conducted experiments in BV2 microglial cells, treating cells with sub-threshold concentrations of MPP+ (0.01-0.02 mmol/L, insufficient to induce significant microglial activation or cytokine secretion) while silencing SENP1. Subsequently, IL-6 and TNF-α secretion was detected using Absin ELISA kits.

(2) Product Function and Experimental Value

• Precise Quantification: Absin ELISA kits exhibit high specificity and sensitivity, enabling accurate detection of low-concentration IL-6 and TNF-α in cell supernatants, providing reliable quantitative data for assessing microglial inflammatory responses.
• Pathway Function Validation: Experimental results demonstrated that SENP1 silencing significantly increased IL-6 and TNF-α secretion in BV2 cells even under sub-threshold MPP+ treatment (Fig. S2). This finding robustly establishes the critical role of the AMPK-SENP1-Sirt3 pathway in suppressing microglial inflammatory responses, further elucidating its function in PD pathogenesis.

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