TAT-PPA1 protects against oxidative stress-induced loss of dopaminergic neurons.

Mol Cell Neurosci

Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address:

Published: December 2024

AI Article Synopsis

  • Parkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopamine-producing neurons in the brain, leading to major motor issues.
  • The research introduces a new protein, TAT-PPA1, that can easily enter cells and brain tissue, showing no toxicity while protecting against damage caused by a toxin linked to PD.
  • TAT-PPA1 helps improve cell survival by inhibiting specific signaling pathways and reduces cell death, demonstrating potential as a treatment to enhance motor functions in PD models.

Article Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in severe motor impairments. Inorganic pyrophosphatase 1 (PPA1) plays a key role in various biological processes, and this study introduces a cell-penetrating PPA1 fusion protein (TAT-PPA1) to explore its transduction into cells and brain tissues. TAT-PPA1 effectively penetrates SH-SY5Y cells and the SN region of PD animal models without toxicity, exhibiting protective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-)-induced cell death. TAT-PPA1 revealed an inhibitory influence on the MAPK signaling pathway and MPTP-induced reactive oxygen species (ROS) production. TAT-PPA1 suppresses JNK, AKT, p53, ERK, and p38 phosphorylation, showcasing its multifaceted role in cell survival pathways. In the MPTP-induced PD animal model, TAT-PPA1 prevents dopaminergic cell death and enhances motor function. This study shows that TAT-PPA1 protects against oxidative stress and cell death in neurodegenerative diseases, suggesting potential as a PD treatment.

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Source
http://dx.doi.org/10.1016/j.mcn.2024.103978DOI Listing

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