Teaching the basics of repurposing mitochondria-targeted drugs: From Parkinson's disease to cancer and back to Parkinson's disease. Redox Biol 2020 Sep;36:101665
Date
08/17/2020Pubmed ID
32795938Pubmed Central ID
PMC7426584DOI
10.1016/j.redox.2020.101665Scopus ID
2-s2.0-85089281502 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Parkinson's disease (PD) and cancer share common mutations in mitochondrial proteins: Parkin and PINK1. The overlapping of genes involved in PD and cancer implies that the two diseases might share a common pathogenic mechanism. There are other compelling rationales for a mechanistic link between these diseases. Mitochondria and autophagy/mitophagy are emerging as therapeutic targets in PD and cancer: Ongoing research in our laboratories has shown that, when administered early, mitochondria-targeted agents afford neuroprotection in preclinical mice models of PD. Also, we discovered that mitochondria-targeted drugs inhibit tumor cell proliferation. We propose that mitochondrial targeting stimulates conservation of cellular energy critical for neuronal cell survival, whereas the energy conservation mechanism inhibits proliferation of cancer cells by depriving the energy necessary for cancer cell growth. We propose a promising drug repurposing strategy involving mitochondria-targeted drugs synthesized from naturally occurring molecules and FDA-approved drugs that are relatively nontoxic in both PD and cancer. These compounds have been shown to induce various cellular signaling pathways for autophagy/mitophagy, anti-inflammatory, and immunomodulatory effects that are implicated as therapeutic mechanisms in PD and cancer.
Author List
Kalyanaraman BAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDrug Repositioning
Mice
Mitochondria
Neoplasms
Parkinson Disease
Pharmaceutical Preparations
Protein Kinases
