title: Are the endocannabinoid-like compounds N-acyl aminoacids neuroprotective after traumatic brain injury?
abstract: In recent years, a library of approx. 70 N-acyl aminoacids (NAAAs) was discovered in the rat brain. A particular member of this family of compounds is arachidonoyl serine (AraS), which has generated special interest as a potential therapy for traumatic brain injury (TBI). This is due to its structural similarity to the endocannabinoid (eCB) 2-arachidonoyl glycerol (2-AG), which was previously shown to be beneficial in the recovery in a closed head injury model of TBI. Indeed, AraS exerted eCB-mediated neuroprotection, which was evident in numerous aspects related to the secondary damage characterizing TBI. These findings promoted broadening of the research to additional compounds of the NAAA family that share a structural similarity to AraS, namely, palmitoyl serine (PalmS) and oleoyl serine. The latter did not exhibit any improvement in recovery, whereas the former displayed some neuroprotection, albeit inferior to 2-AG and AraS, via unknown mechanisms. Interestingly, when a combined treatment of 2-AG, AraS and PalmS was tested, the overall effect on the severity score was inferior to their individual effects, suggesting not only a lack of direct or indirect synergism, but also possibly some spatial hindrance. Taken together, the complexity of the damage caused by TBI and the many open questions concerning the role of the eCB system in health and disease, the findings so far may serve as a small trace to the understanding of the eCB system, as well as of the mechanisms underlying TBI.
authors.forename: Aniv
authors.initials: A
authors.lastname: Mann
authors.forename: Ayelet
authors.initials: A
authors.lastname: Cohen-Yeshurun
authors.forename: Victoria
authors.initials: V
authors.lastname: Trembovler
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000596:Amino Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy*; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D005989:Glycerides / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; C094503:glyceryl 2-arachidonate