Effect of Neuroinflammation on Mitochondrial Quality Control Pathways in Parkinson’s Disease – Affected Neurons

Abstract

Parkinson’s disease is characterized by motor dysfunction, which is attributed to the loss of dopaminergic neurons in the midbrain. It is currently thought that inflammation of the brain (neuroinflammation) and defects in ‘mitophagy’, a mitochondrial quality control pathway, contribute significantly to the development of the disease. However, the relationship between these processes is poorly understood. Previous studies have shown that the mitophagic regulatory protein, PINK1, is regulated at the transcriptional level by pro-inflammatory NF-kB transcription factors, implying that neuroinflammation could alter PINK1 expression, thereby compromising the normal operation of the mitophagy pathway. To investigate this we measured the effect of inflammatory cytokines on the steady-state levels of essential mitophagic regulatory proteins and the kinetics of mitophagy using a combination of immunoblotting and live cell imaging. Our data provides new insights into the relationship between neuroinflammation and mitophagy in Parkinson’s disease.