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

Benjamin Matís Pizarro-Galleguillos; Liesa Kunert; Norbert Brüggemann; Jannik Prasuhn

doi:10.3390/antiox12071411

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

Antioxidants (Basel). 2023 Jul 12;12(7):1411. doi: 10.3390/antiox12071411.

Authors

Benjamin Matís Pizarro-Galleguillos^{1

2

3

4}, Liesa Kunert^{2

3

4}, Norbert Brüggemann^{2

4}, Jannik Prasuhn^{2

3

4

5

6}

Affiliations

¹ Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile.
² Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, 23562 Lübeck, Germany.
³ Institute of Neurogenetics, University of Lübeck, 23562 Lübeck, Germany.
⁴ Center for Brain, Behavior, and Metabolism, University of Lübeck, 23562 Lübeck, Germany.
⁵ Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁶ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21287, USA.

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.

Keywords: Parkinson’s disease; TSPO; magnetic resonance imaging (MRI); magnetic resonance spectroscopy imaging (MRSI); mitochondria; mitochondrial dysfunction; neuroimaging; neuroinflammation; positron emission tomography (PET) imaging.

Publication types

Review

Grants and funding

B.M.P.-G. was supported by the Global Parkinson’s Genetics Program (GP2). GP2 is funded by the Aligning Science Across Parkinson’s (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson’s Research. For a complete list of GP2 members see https://gp2.org/. He also receeived the Chilean National ANID Ph.D. scholarship (2020). N.B. received funding from the Deutsche Forschungsgemeinschaft (BR4328.2-1 [FOR2488], GRK1957), the Michael J. Fox Foundation, and the EU Joint Programme—Neurodegenerative Disease Research (JPND). J.P. received funding from the Parkinson’s Foundation, the Deutsche Parkinsongesellschaft, the Thiemann Stiftung, and the Deutsche Forschungsgemeinschaft via the Clinician Scientist School Lübeck (DFG-GEPRIS 413535489).