LncRNA MALAT1 targeting miR-124-3p regulates DAPK1 expression contributes to cell apoptosis in Parkinson's Disease

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Death Associated Protein Kinase 1 (DAPK1) is implicated in central nervous system disorders, including Parkinson's disease (PD).
• The precise molecular mechanisms of DAPK1's role in PD pathogenesis are not fully understood.

Purpose of the Study:

• To investigate the regulatory mechanisms of DAPK1 in Parkinson's disease.
• To explore the potential involvement of long non-coding RNA MALAT1 and microRNA-124-3p (miR-124-3p) in DAPK1-mediated PD pathology.

Main Methods:

• Utilized MPP+ treated SH-SY5Y cells and MPTP-induced Parkinson's disease mouse models.
• Assessed the expression levels of DAPK1, MALAT1, and miR-124-3p.
• Manipulated MALAT1 and miR-124-3p levels using knockdown and mimics/inhibitors, respectively.
• Evaluated cell apoptosis and motor function.

Main Results:

• DAPK1 expression was upregulated and negatively correlated with miR-124-3p in MPP+-treated cells.
• Inhibition of DAPK1 by miR-124-3p mimics reduced apoptosis.
• Knockdown of MALAT1 decreased DAPK1 levels and apoptosis, an effect reversed by miR-124-3p inhibition.
• MALAT1 knockdown improved motor function and reduced apoptosis in PD mice via miR-124-3p upregulation and DAPK1 downregulation.

Conclusions:

• Long non-coding RNA MALAT1 positively regulates DAPK1 expression by sponging miR-124-3p.
• The MALAT1/miR-124-3p/DAPK1 signaling pathway plays a critical role in mediating cell apoptosis and motor disorders in Parkinson's disease.
• This pathway represents a potential therapeutic target for PD treatment.