Iron- and Neuromelanin-Weighted Neuroimaging to Study Mitochondrial Dysfunction in Patients with Parkinson's Disease

Int J Mol Sci. 2022 Nov 8;23(22):13678. doi: 10.3390/ijms232213678.

Abstract

The underlying causes of Parkinson's disease are complex, and besides recent advances in elucidating relevant disease mechanisms, no disease-modifying treatments are currently available. One proposed pathophysiological hallmark is mitochondrial dysfunction, and a plethora of evidence points toward the interconnected nature of mitochondria in neuronal homeostasis. This also extends to iron and neuromelanin metabolism, two biochemical processes highly relevant to individual disease manifestation and progression. Modern neuroimaging methods help to gain in vivo insights into these intertwined pathways and may pave the road to individualized medicine in this debilitating disorder. In this narrative review, we will highlight the biological rationale for studying these pathways, how distinct neuroimaging methods can be applied in patients, their respective limitations, and which challenges need to be overcome for successful implementation in clinical studies.

Keywords: Parkinson’s disease; iron; magnetic resonance imaging (MRI); magnetic resonance spectroscopy imaging (MRSI); mitochondria; neuroimaging; neuromelanin.

Publication types

  • Review

MeSH terms

  • Humans
  • Iron / metabolism
  • Mitochondria / metabolism
  • Neuroimaging
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / metabolism

Substances

  • neuromelanin
  • Iron

Grants and funding

B.M.P.G. has received funding from the GP2 (Global Parkinson’s Genetics Programm)—Underrepresented populations (UPR) consortium and the Chilean National ANID Ph.D. scholarship (2020). N.B. received funding from the Deutsche Forschungsgemeinschaft (BR4328.2-1 [FOR2488], GRK1957), and the Michael J. Fox Foundation. J.P. received funding from the Parkinson’s Foundation, the Deutsche Parkinsongesellschaft, and the Deutsche Forschungsgemeinschaft via the Clinician Scientist School Lübeck (DFG-GEPRIS 413535489).