Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics.
At a glance
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This study shows that CB1 receptor coupling efficacy in glutamatergic neurons is greater than in GABAergic neurons, providing evidence for an additional level of complexity in the differential signalling measured for this GPCR depending on the cell type.
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The first study showing different time-dependent changes in anandamide and 2-AG levels, and a dual beneficial and exacerbating action on disease signs by endocannabinoids, in a model of amyloid-β-induced toxicity.
- Molecular reorganization of endocannabinoid signalling in Alzheimer's disease. Brain. 134, 1041–1060 (2011).
This study, along with Ref. 147 identifies increased 2-AG levels as a possible maladaptive mechanism contributing to some signs in amyloid-β-induced toxicity.
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- Fatty acid amide hydrolase (FAAH) inhibition reduces L-3,4-dihydroxyphenylalanine-induced hyperactivity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned non-human primate model of Parkinson's disease. J. Pharmacol. Exp. Ther. 336, 423–430 (2011). et al.
- Cannabinoid receptor 2 signaling in peripheral immune cells modulates disease onset and severity in mouse models of Huntington's disease. J. Neurosci. 32, 18259–18268 (2012). et al.
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- Supplementary information S1 (table) (362 KB)
The “endocannabinoidome”. Endocannabinoids, endocannabinoid-related mediators and their metabolic enzymes and receptors.