# The role of natural killer cells in Parkinson’s disease

## TL;DR

This paper reviews how natural killer cells may help reduce inflammation and α-synuclein buildup in Parkinson’s disease, suggesting new treatment possibilities.

## Contribution

The paper highlights the novel role of natural killer cells in degrading α-synuclein aggregates and modulating inflammation in Parkinson’s disease.

## Key findings

- Natural killer cells can degrade α-synuclein aggregates, a key component in Parkinson’s disease pathology.
- Systemic depletion of natural killer cells worsens neuropathology in mouse models of Parkinson’s disease.
- Natural killer cells may reduce inflammation and α-synuclein burden in affected brain regions.

## Abstract

Numerous lines of evidence indicate an association between sustained inflammation and Parkinson’s disease, but whether increased inflammation is a cause or consequence of Parkinson’s disease remains highly contested. Extensive efforts have been made to characterize microglial function in Parkinson’s disease, but the role of peripheral immune cells is less understood. Natural killer cells are innate effector lymphocytes that primarily target and kill malignant cells. Recent scientific discoveries have unveiled numerous novel functions of natural killer cells, such as resolving inflammation, forming immunological memory, and modulating antigen-presenting cell function. Furthermore, natural killer cells are capable of homing to the central nervous system in neurological disorders that exhibit exacerbated inflammation and inhibit hyperactivated microglia. Recently, a study demonstrated that natural killer cells scavenge alpha-synuclein aggregates, the primary component of Lewy bodies, and systemic depletion of natural killer cells results in exacerbated neuropathology in a mouse model of alpha-synucleinopathy, making them a highly relevant cell type in Parkinson’s disease. However, the exact role of natural killer cells in Parkinson’s disease remains elusive. In this review, we introduce the systemic inflammatory process seen in Parkinson’s disease, with a particular focus on the direct and indirect modulatory capacity of natural killer cells in the context of Parkinson’s disease.

Understanding the roles that inflammation and immune cells called natural killer (NK) cells play in Parkinson’s disease (PD) may help in finding new treatments. In PD, a neurodegenerative disease, the protein α-synuclein is misshapen and accumulates in brain cells, causing inflammation. NK cells, which mostly target cancer cells, have recently been shown to resolve inflammation. Jae-Kyung Lee and Rachael H. Earls of the University of Georgia College of Veterinary Medicine, Athens, USA, reviewed the role of NK cells in PD. They report that NK cells can degrade α-synuclein aggregates. Further, NK cells are recruited to areas of inflammation where they then decrease the α-synuclein burden and reduce inflammation. Although further research is needed to understand how age and PD affect NK cell number and functions, these results may illuminate pathways to better treatments for PD.