One of the factors known to underlie all forms of glaucoma (as well as other neurodegenerative diseases) is mitochondrial dysfunction. The mitochondria are commonly called the "energy factories of the cells." Optic nerve and brain cells have high energy requirements and are therefore highly dependent upon healthy mitochondrial function. With that in mind, you will recognize the positive implications of this study on CBN (including its relevance to glaucoma).
Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors
The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration.
It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function.
Previously, we identified cannabinol (CBN) as a potent neuroprotector.
Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors.
Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis.
These protective effects of CBN are at least partly mediated by the promotion of endogenous antioxidant defenses and the activation of AMP-activated protein kinase (AMPK) signaling.
Together, our data highlight the potential of mitochondrially-targeted compounds such as CBN as novel oxytotic/ferroptotic inhibitors to rescue mitochondrial dysfunction as well as opportunities for the discovery and development of future neurotherapeutics.
Keywords: AMPK; Aging; Antioxidant defense; Cannabinoid; Mitochondrial dysfunction; Neurodegenerative disease; Neurotherapeutics; Oxytosis/ferroptosis.
- Journal: Free Radic Biol Med. 2022 May 1;184:16.
- doi: 10.1016/j.freeradbiomed.2022.03.022.
- Epub 2022 Apr 2.
- PMID: 35381547
- Free PMC article? No