Neuroinflammation and Mitochondrial Dysfunction in Parkinson’s Disease: Connecting Neuroimaging with Pathophysiology

Abstract

There is a pressing need for disease-modifying therapies in patients suffering from neurodegenerative diseases, including Parkinson’s disease (PD). However, these disorders face unique challenges in clinical trial designs to assess the neuroprotective properties of potential drug candidates. One of these challenges relates to the often unknown individual disease mechanisms that would, however, be relevant for targeted treatment strategies. Neuroinflammation and mitochondrial dysfunction are two proposed pathophysiological hallmarks and are considered to be highly interconnected in PD. Innovative neuroimaging methods can potentially help to gain deeper insights into one’s predominant disease mechanisms, can facilitate patient stratification in clinical trials, and could potentially map treatment responses. This review aims to highlight the role of neuroinflammation and mitochondrial dysfunction in patients with PD (PwPD). We will specifically introduce different neuroimaging modalities, their respective technical hurdles and challenges, and their implementation into clinical practice. We will gather preliminary evidence for their potential use in PD research and discuss opportunities for future clinical trials.

Exploring neurodegenerative disorders using advanced magnetic resonance imaging of the glymphatic system

“…Imaging techniques from these modalities allow visualization of the glymphatic pathways and quantification of the clearance of solutes from the brain, thus providing valuable insights into possible coping mechanisms in PwND ( 7 , 25 ). The potential of neuroimaging in establishing new treatment options for PwND is immense ( 27 – 29 ). Visualizing and quantifying the glymphatic system in vivo can provide an earlier diagnosis of conditions associated with glymphatic dysfunction.…”

“…Visualizing and quantifying the glymphatic system in vivo can provide an earlier diagnosis of conditions associated with glymphatic dysfunction. Earlier diagnosis is crucial for effectively managing these conditions, as it allows for the timely initiation of disease-modifying treatments as soon as they become available ( 27 – 29 ). Furthermore, neuroimaging can provide a means to measure the effectiveness of treatments to enhance glymphatic function ( 6 , 10 , 24 ).…”

Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson’s Disease

“…Neuroinflammation is characterized as an inflammatory response of brain tissue caused by immune cells and the mediators that they release, such as chemokines, cytokines, ROS, and additional secondary transmitters [355][356][357][358]. Neuroinflammation is also caused by environmental factors and genes which significantly impact immune system activation and modification.…”

The Role of Immune Dysfunction in Parkinson’s Disease Development

“…In addition, inflammation driven by dysfunctional mitochondria can occur in the context of aging, as mitochondria play a critical role during the pro-inflammatory response against pathogenic infections [89], and neuroinflammation-related mitochondrial dysfunction occurs in different neurodegenerative disorders such as PD [90].…”