Cell Death Differ: ARRB1 and ARRB2 show opposite functions in microglia-mediated inflammation and Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD), which affects 2-3% of the global population over 65 years old.
Although the etiology and pathogenesis of PD are not yet fully understood, previous studies have shown that exposure to a variety of genetic factors and the environment can lead to the progression of PD.
These possible mechanisms include dopamine metabolism, mitochondrial dysfunction, and endoplasmic reticulum response.
change shock, autophagy and impaired immune reduced force.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD), which affects 2-3% of the global population over 65 years old.
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD), which affects 2-3% of the global population over 65 years old.
immunity

Microglia are the main immune cells of the brain, and current studies have confirmed that they are related to the inflammatory response activated in PD.
Therefore, identifying the regulators involved in the activity of microglia may provide new possibilities for the design of drugs for the treatment of PD.

Previous studies have confirmed that ARRB (β-arrestin) has different roles in the pathogenesis of central nervous system diseases.
Although ARRB can regulate a variety of physiological and pathological processes, its function and regulation in PD are still unclear.

In this study, the researchers found that in the PD mouse model, especially in microglia, the expression of ARRB1 (β-arrestin1) and ARRB2 (β-arrestin2) are mutually regulated.

Knockout of ARRB1 will improve the pathological features of PD, including the loss of dopaminergic neurons in the body, neuroinflammation and activation of microglia, and neuronal damage mediated by microglia, while Knockout of ARRB2 will aggravate related pathology feature.

Expression of ARRB1 and ARRB2 in PD mouse model

Researchers have found that in primary cultured microglia and macrophages, ARRB1 and ARRB2 have an adverse effect on the inflammatory response and the activation of inflammatory STAT1 and NF-κB pathways, and the two ARRB proteins can compete with each other.
The activated form of p65 (a member of the NF-κB signaling pathway) interacts with each other.

Further studies have shown that ARRB1 and ARRB2 can differentially regulate the expression of Nprl3, such as the results of RNA sequencing.

In the study of gain and loss of function, Nprl3 can regulate the function of two ARRB proteins in the inflammatory response of microglia.

Related schematics

All in all, the results of this study show that two closely related ARRBs play opposite functions in microglia-mediated inflammation and the pathogenesis of PD, and these functions are partly mediated by Nprl3.

This study also provides novel insights into the functional differences of ARRB in PD.

The two closely related ARRBs play opposite functions in the microglia-mediated inflammation and the pathogenesis of PD, and these functions are partly mediated by Nprl3.

org/10.

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