Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid

Raman, Chandrasekaran; McAllister, Sean D.; Rizvi, Gulrukh; Patel, Shetal; Moore, Dan H.; Abood, Mary E.

doi:10.1080/14660820310016813

Cited by 118 publications

(94 citation statements)

References 22 publications

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“…The model was developed in the 1990s and was used to investigate the effects of Δ 9 -THC [154], cannabinol [155], WIN55,212-2 [156], and the selective CB 2 R agonist AM1241 [157,158]. This solid pharmacological evidence is also supported by data collected from double mutants generated by crossing SOD-1 mutant mice with some of the different mice deficient in endocannabinoid genes (e.g., FAAH -/-, CB 1 -/-), which not only reinforced the interest of CB 1 R agonists, but also the elevation of endocannabinoid levels with FAAH inhibitors [156].…”

Section: Cannabinoids and Chronic Neurodegenerative Disorders: IV Alsmentioning

confidence: 99%

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

2015

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Cannabinoids form a singular family of plantderived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells). This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer's disease, Parkinson's disease, Huntington's chorea, and amyotrophic lateral sclerosis. This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression, despite the fact that the few clinical trials conducted so far with these medicines have failed to demonstrate beneficial effects.

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Section: Cannabinoids and Chronic Neurodegenerative Disorders: IV Alsmentioning

confidence: 99%

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

2015

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“…Beneficial effects of THC have been reported in studies of animal models of several neurodegenerative disorders. For example, THC attenuated the disease process and prolonged survival in a mouse model of amyotrophic lateral sclerosis (Raman et al, 2004). THC protected cultured neuronal cells Gilbert et al, 2007) and retinal neurons (El-Remessy et al, 2003) against excitotoxic damage.…”

Section: Subtoxic Doses Of Phytochemicals Can Protect Neurons Againstmentioning

confidence: 99%

Viewpoint: Mechanisms of Action and Therapeutic Potential of Neurohormetic Phytochemicals

Mattson¹,

Son²,

Camandola³

2007

Dose-Response

127

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ᮀ The nervous system is of fundamental importance in the adaptive (hormesis) responses of organisms to all types of stress, including environmental "toxins". Phytochemicals present in vegetables and fruits are believed to reduce the risk of several major diseases including cardiovascular disease, cancers and neurodegenerative disorders. Although antioxidant properties have been suggested as the basis of health benefits of phytochemicals, emerging findings suggest a quite different mechanism of action. Many phytochemicals normally function as toxins that protect the plants against insects and other damaging organisms. However, at the relatively low doses consumed by humans and other mammals these same "toxic" phytochemicals activate adaptive cellular stress response pathways that can protect the cells against a variety of adverse conditions. Recent findings have elucidated hormetic mechanisms of action of phytochemicals (e.g., resveratrol, curcumin, sulforaphanes and catechins) using cell culture and animal models of neurological disorders. Examples of hormesis pathways activated by phytochemicals include the transcription factor Nrf-2 which activates genes controlled by the antioxidant response element, and histone deacetylases of the sirtuin family and FOXO transcription factors. Such hormetic pathways stimulate the production of antioxidant enzymes, protein chaperones and neurotrophic factors. In several cases neurohormetic phytochemicals have been shown to suppress the disease process in animal models relevant to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, and can also improve outcome following a stroke. We are currently screening a panel of biopesticides in order to establish hormetic doses, neuroprotective efficacy, mechanisms of action and therapeutic potential as dietary supplements.

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“…The growing list includes potential treatments for chemotherapy complications (Sharma et al, 2005), tumor growth (Bifulco et al, 2004), pain (Calignano et al, 1998), Parkinson's disease (Maccarrone et al, 2003;FernandezEspejo et al, 2004), Huntington's disease (Lastres-Becker et al, 2002), Alzheimer's disease (Ramirez et al, 2005), multiple sclerosis (Mestre et al, 2005), amyotrophic lateral sclerosis (Raman et al, 2004), glaucoma (El-Remessy et al, 2003), as well as traumatic brain injury (Panikashvili et al, 2001), cerebral ischemia (Nagayama et al, 1999), and other excitotoxic insults (Shen and Thayer, 1998;Marsicano et al, 2003). The protective effects may involve signal transduction pathways linked to cannabinoid CB 1 receptors that recognize the endocannabinoids anandamide and 2-arachidonylglycerol (Bouaboula et al, 1995;Derkinderen et al, 1998Derkinderen et al, , 2003Galve-Roperh et al, 2002;Karanian et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Karanian¹,

Brown²,

Makriyannis³

et al. 2005

J. Neurosci.

114

109

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The endocannabinoid system has been suggested to elicit signals that defend against several disease states including excitotoxic brain damage. Besides direct activation with CB 1 receptor agonists, cannabinergic signaling can be modulated through inhibition of endocannabinoid transport and fatty acid amide hydrolase (FAAH), two mechanisms of endocannabinoid inactivation. To test whether the transporter and FAAH can be targeted pharmacologically to modulate survival/repair responses, the transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) and the FAAH inhibitor palmitylsulfonyl fluoride (AM374) were assessed for protection against excitotoxicity in vitro and in vivo. AM374 and AM404 both enhanced mitogen-activated protein kinase (MAPK) activation in cultured hippocampal slices. Interestingly, combining the distinct inhibitors produced additive effects on CB 1 signaling and associated neuroprotection. After an excitotoxic insult in the slices, infusing the AM374/AM404 combination protected against cytoskeletal damage and synaptic decline, and the protection was similar to that produced by the stable CB 1 agonist AM356 (R-methanandamide). AM374/ AM404 and the agonist also elicited cytoskeletal and synaptic protection in vivo when coinjected with excitotoxin into the dorsal hippocampus. Correspondingly, potentiating endocannabinoid responses with the AM374/AM404 combination prevented behavioral alterations and memory impairment that are characteristic of excitotoxic damage. The protective effects mediated by AM374/AM404 were (1) evident 7 d after insult, (2) correlated with the preservation of CB 1 -linked MAPK signaling, and (3) were blocked by a selective CB 1 antagonist. These results indicate that dual modulation of the endocannabinoid system with AM374/AM404 elicits neuroprotection through the CB 1 receptor. The transporter and FAAH are modulatory sites that may be exploited to enhance cannabinergic signaling for therapeutic purposes.

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Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid

Cited by 118 publications

References 22 publications

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

Viewpoint: Mechanisms of Action and Therapeutic Potential of Neurohormetic Phytochemicals

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

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