Get high, protect your brain? 😊 Maybe it only helps the famous fruit fly? 😊
"... Scientists have begun exploring whether cannabinoids—compounds derived from the cannabis plant, like well-known THC (tetrahydrocannabinol) and CBD (cannabidiol)—may offer a solution. A third, lesser-known cannabinoid called CBN (cannabinol) has recently piqued the interest of researchers, who have begun exploring the clinical potential of the milder, less psychoactive substance. ...
In a new study, scientists at the Salk Institute help explain how CBN protects the brain against aging and neurodegeneration, then use their findings to develop potential therapeutics. The researchers created four CBN-inspired compounds that were more neuroprotective than the standard CBN molecule—one of which was highly effective in treating traumatic brain injury in a Drosophila fruit fly model. ..."
In a new study, scientists at the Salk Institute help explain how CBN protects the brain against aging and neurodegeneration, then use their findings to develop potential therapeutics. The researchers created four CBN-inspired compounds that were more neuroprotective than the standard CBN molecule—one of which was highly effective in treating traumatic brain injury in a Drosophila fruit fly model. ..."
From the highlights and abstract:
"Highlights
• Fragment-based approach to analyze the structure-activity relationship of phytocannabinoids against oxytosis/ferroptosis.
• Development of novel analogs of cannabinol (CBN) with improved CNS druglikeness and antioxidant activities.
• New CBN analogs are potent inhibitors of oxytosis/ferroptosis in cell-based phenotypic screening.
• New CBN analogs prevent mitochondrial dysfunction in neuronal cells.
• New CBN analogs show in vivo beneficial efficacy in the Drosophila model of mild traumatic brain injury (mTBI).
Abstract
The oxytosis/ferroptosis regulated cell death pathway is an emerging field of research owing to its pathophysiological relevance to a wide range of neurological disorders, including Alzheimer's and Parkinson's diseases and traumatic brain injury. Developing novel neurotherapeutics to inhibit oxytosis/ferroptosis offers exciting opportunities for the treatment of these and other neurological diseases. Previously, we discovered cannabinol (CBN) as a unique, potent inhibitor of oxytosis/ferroptosis by targeting mitochondria and modulating their function in neuronal cells. To further elucidate which key pharmacophores and chemical space are essential to the beneficial effects of CBN, we herein introduce a fragment-based drug discovery strategy in conjunction with cell-based phenotypic screens using oxytosis/ferroptosis to determine the structure-activity relationship of CBN. The resulting information led to the development of four new CBN analogs, CP1-CP4, that not only preserve the sub-micromolar potency of neuroprotection and mitochondria-modulating activities seen with CBN in neuronal cell models but also have better druglike properties. Moreover, compared to CBN, the analog CP1 shows improved in vivo efficacy in the Drosophila model of mild traumatic brain injury. Together these studies identify the key molecular scaffolds of cannabinoids that contribute to neuroprotection against oxytosis/ferroptosis. They also highlight the advantageous approach of combining in vitro cell-based assays and rapid in vivo studies using Drosophila models for evaluating new therapeutic compounds."
Graphical abstract
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