EMBL Grenoble researchers investigated the interaction between THC and some proteins in a recent study published in Life Science Alliance. The researchers showed in vitro that THC inhibits the human enzyme autotaxin. In vivo studies are required to confirm that autotaxin and THC binding is associated with the therapeutic effects of THC administration.
Autotaxin plays an essential role in many cellular functions. It can be found in most body fluids and is critical for murine embryonic vessel formation. Autotaxin specifically produces a molecule called lysophosphatidic acid (LPA) which proliferates cells. If LPA production is disrupted, it can cause cancer, inflammation, or pulmonary fibrosis. LPA is an important signaling phospholipid with the potential to bind to six G protein-coupled receptors (LPA1–6). The ATX-LPA signaling axis is a critical factor in many physiological and pathophysiological conditions. Understanding cannabis on a molecular level can highlight the most effective ways to optimize autotaxin.
The gene product of autotaxin can exist in at least three isoforms (ATX-α, ATX-β, and ATX-γ). ATX-γ is considered the “brain-specific” isoform implicated with neuronal disorders, including multiple sclerosis, depression, neuropathic pain, and Alzheimer’s disease.
The research team obtained the three-dimensional structure of the THC cannabinoid bound with autotaxin during the investigation. By observing the interaction between THC and proteins and employing macromolecular crystallography, the researchers could examine the molecular basis of how THC binds with autotaxin and its potential in medical cannabis therapy.
The study demonstrated in vitro inhibition effects on the catalysis of ATX with different substrates and the capability of THC to significantly modulate LPA signaling. Understanding how THC and other cannabinoids interact in human cells at the atomic level will lead to more effective cannabinoid product development.
Sources: EMBL, Eureka News Alert, Life Science Alliance