The Influence of Cannabinoids on <i>Drosophila</i> Behaviors, Longevity, and Traumatic Injury Responses of the Adult Nervous System

Candib, Alec; Lee, Nicholas; Sam, Natasha; Cho, Eddie; Rojas, Jesse; Hastings, Reina; DeAlva, Kyle; Khon, Diana; Gonzalez, Andrea; Molina, Brandon; Torabzadeh, Gina; Vu, Josephine; Hasenstab, Kyle; Sant, Karylin; Phillips, Joy A.; Finley, Kim

doi:10.1089/can.2022.0285

Cited by 3 publications

(5 citation statements)

References 54 publications

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“…As non-mammalian models, they have some limitations as well as enormous values in early biomedical research [ 49 , 50 ]. We recently reported that using our Drosophila model of mild traumatic brain injury (mTBI), phytocannabinoids, including cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC), were also neuroprotective [ 18 , 19 ]. Together, the Drosophila mTBI model can serve as a rapid, inexpensive, and highly effective tool to screen and evaluate the in vivo therapeutic potential of additional, cannabinoid-based compounds under conditions of acute and protracted neural stress.…”

Section: Discussionmentioning

confidence: 99%

“…Drosophila Stocks and Culturing Conditions. The assay procedure has been previously described [ 18 , 19 ]. Briefly, adult wild-type Drosophila melanogaster Canton-S and w 1118 stock lines were obtained from the Bloomington Drosophila Stock Center.…”

Section: Methodsmentioning

confidence: 99%

“…Cohorts were transferred to vials containing standard fly media (0.1% ethanol), or defined dosages (μM) of compounds (0.1% ethanol). The dosage range for the compounds was based on published Drosophila findings [ 19 ]. A 5 mg dose for adult flies is equivalent to about 16 μmol for the compounds or about 0.212 μM final concentration for a whole-body human (about 75 kg) dose.…”

Section: Methodsmentioning

confidence: 99%

“…Drosophila Mild Traumatic Brain Injury (mTBI) Model. TBI methods used for this study have been previously described [ 18 , 19 ]. Briefly, pretreated flies were anesthetized, placed in 2 mL screw cap tubes (10 flies/tube), and allowed to recover before being placed in the Omni Bead Ruptor-24 homogenizer (Omni International, Kennesaw, GA).…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, pretreated flies were anesthetized, placed in 2 mL screw cap tubes (10 flies/tube), and allowed to recover before being placed in the Omni Bead Ruptor-24 homogenizer (Omni International, Kennesaw, GA). Adult control and treated flies were pretreated for 3 days with different compounds before exposure to 10 mild trauma bouts (mild traumatic brain injury [mTBI] 10x, 2.1 m/s) at 1 week of age [ 19 ]. Following injury, flies were returned to vials containing treated media and maintained using standard culturing conditions.…”

Section: Methodsmentioning

confidence: 99%

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Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytosis/ferroptosis for neurological disorders

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et al. 2024

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytosis/ferroptosis for neurological disorders

Liang,

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Soriano-Castell

et al. 2024

Redox Biology

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Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans

Wang,

Arnold

2024

GeroScience

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There is a significant global upsurge in the number and proportion of older persons in the population. With this comes an increasing prevalence of age-related conditions which pose a major challenge to healthcare systems. The development of anti-ageing treatments may help meet this challenge by targeting the ageing process which is a common denominator to many health problems. Cannabis-like compounds (cannabinoids) are reported to improve quality of life and general well-being in human trials, and there is increasing preclinical research highlighting that they have anti-ageing activity. Moreover, preclinical evidence suggests that endogenous cannabinoids regulate ageing processes. Here, we review the anti-ageing effects of the cannabinoids in various model systems, including the most extensively studied nematode model, Caenorhabditis elegans. These studies highlight that the cannabinoids lengthen healthspan and lifespan, with emerging evidence that they may also hinder the development of cellular senescence. The non-psychoactive cannabinoid cannabidiol (CBD) shows particular promise, with mechanistic studies demonstrating it may work through autophagy induction and activation of antioxidative systems. Furthermore, CBD improves healthspan parameters such as diminishing age-related behavioural dysfunction in models of both healthy and accelerated ageing. Translation into mammalian systems provides an important next step. Moreover, looking beyond CBD, future studies could probe the multitude of other cannabis constituents for their anti-ageing activity.

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Mitophagy-promoting agents and their ability to promote healthy-aging

Srivastava,

Gross

2023

Biochemical Society Transactions

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The removal of damaged mitochondrial components through a process called mitochondrial autophagy (mitophagy) is essential for the proper function of the mitochondrial network. Hence, mitophagy is vital for the health of all aerobic animals, including humans. Unfortunately, mitophagy declines with age. Many age-associated diseases, including Alzheimer's and Parkinson's, are characterized by the accumulation of damaged mitochondria and oxidative damage. Therefore, activating the mitophagy process with small molecules is an emerging strategy for treating multiple aging diseases. Recent studies have identified natural and synthetic compounds that promote mitophagy and lifespan. This article aims to summarize the existing knowledge about these substances. For readers’ convenience, the knowledge is presented in a table that indicates the chemical data of each substance and its effect on lifespan. The impact on healthspan and the molecular mechanism is reported if known. The article explores the potential of utilizing a combination of mitophagy-inducing drugs within a therapeutic framework and addresses the associated challenges of this strategy. Finally, we discuss the process that balances mitophagy, i.e. mitochondrial biogenesis. In this process, new mitochondrial components are generated to replace the ones cleared by mitophagy. Furthermore, some mitophagy-inducing substances activate biogenesis (e.g. resveratrol and metformin). Finally, we discuss the possibility of combining mitophagy and biogenesis enhancers for future treatment. In conclusion, this article provides an up-to-date source of information about natural and synthetic substances that activate mitophagy and, hopefully, stimulates new hypotheses and studies that promote healthy human aging worldwide.

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The Influence of Cannabinoids on Drosophila Behaviors, Longevity, and Traumatic Injury Responses of the Adult Nervous System

Cited by 3 publications

References 54 publications

Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytosis/ferroptosis for neurological disorders

Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytosis/ferroptosis for neurological disorders

Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans

Mitophagy-promoting agents and their ability to promote healthy-aging

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