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RAGE and its emerging role in the pathogenesis of Parkinson's disease
Xiuli Jiang1, Xiaoli Wang1, Miao Tuo1
1Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Abstract:
Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays crucial roles in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE involves in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy. In CNS, RAGE was primarily expressed in neurons, microglia and vascular endothelial cells. Interacting with ligands, RAGE induces a series of signal transduction cascades and leads to the activation of transcription factor NF-κB as well as increased expression of cytokines like TNF-α, IL-1. Moreover, binding to RAGE can also stimulate the generation of reactive oxygen species (ROS), which is implicated in neuron death. It was reported that RAGE were highly expressed in PD patients when compared to age-matched controls. And RAGE ablation protected nigral dopaminergic neurons against cell death in MPTP treated mice. Here we review this article to elucidate the role of RAGE in PD pathogenesis and highlight the anti-RAGE strategies in the treatment of PD.
Insights
Receptor for advanced glycation end products (RAGE) is implicated in Parkinson's disease (PD) pathogenesis. Targeting RAGE may offer new therapeutic strategies for treating PD and related neurodegenerative conditions.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Receptor for advanced glycation end products (RAGE) is an immunoglobulin superfamily receptor involved in numerous human diseases.
- RAGE plays roles in cell processes including neuroinflammation, apoptosis, and autophagy, and is expressed in the central nervous system (CNS) by neurons, microglia, and vascular cells.
Purpose of the Study:
- To review the role of RAGE in Parkinson's disease (PD) pathogenesis.
- To highlight anti-RAGE strategies as potential treatments for PD.
Main Methods:
- Review of existing literature on RAGE function and its involvement in neurodegenerative diseases.
- Analysis of studies investigating RAGE expression in PD patients and animal models.
Main Results:
- RAGE activation leads to signaling cascades, NF-κB activation, increased cytokine expression (TNF-α, IL-1), and reactive oxygen species (ROS) generation, contributing to neuron death.
- RAGE is highly expressed in PD patients, and its ablation protects dopaminergic neurons in MPTP-treated mice.
Conclusions:
- RAGE is a significant factor in PD pathogenesis.
- Targeting RAGE presents a promising therapeutic avenue for PD treatment.