Molecular Neurobiology laboratory, Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Barcelona, Spain.
Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED). Instituto de Salud Carlos III, Madrid, Spain.
Adv Exp Med Biol. 2021;1264:81-92. doi: 10.1007/978-3-030-57369-0_6.
Three prevalent neurodegenerative diseases, Parkinson's, Alzheimer's, and Huntington's are in need of symptomatic relief of slowing disease progression or both. This chapter focuses on the potential of cannabinoids to afford neuroprotection, i.e. avoid or retard neuronal death. The neuroprotective potential of cannabinoids is known from the work in animal models and is mediated by the two cannabinoid receptors (CB/CB) and eventually, by their heteromers, GPR55, orphan receptors (GPR3/GPR6/GPR12/GPR18), or PPARγ. Now, there is the time to translate the findings into patients. The chapter takes primarily into account advances since 2016 and addresses the issue of proving neuroprotection in humans. One recent discovery is the existence of activated microglia with neuroprotective phenotype; cannabinoids are good candidates to skew phenotype, especially via glial CB receptors (CBR), whose targeting has, a priori, less side effects those targeting the CBs receptor (CBR), which are expressed in both neurons and glia. The fact that a cannabis extract (SativexTM) is approved for human therapy, such that cannabis use will likely be legalized in many countries and different possibilities that cannabinoid pharmacology suggests a successful route of cannabinoids (natural or synthetic) all the way to be approved and used in the treatment of neurodegeneration.
三种常见的神经退行性疾病,帕金森氏症、阿尔茨海默氏症和亨廷顿氏症,都需要缓解症状和减缓疾病进展。本章重点介绍大麻素具有神经保护作用的潜力,即避免或延缓神经元死亡。大麻素的神经保护潜力来自于动物模型的研究,由两种大麻素受体(CB/CB)介导,最终由它们的异源二聚体、GPR55、孤儿受体(GPR3/GPR6/GPR12/GPR18)或 PPARγ介导。现在,是时候将这些发现转化为患者了。本章主要考虑了 2016 年以来的进展,并探讨了在人类中证明神经保护作用的问题。最近的一项发现是存在具有神经保护表型的激活小胶质细胞;大麻素是改变表型的良好候选物,特别是通过胶质细胞 CB 受体(CBR),靶向 CBR 比靶向 CB 受体(CBR)具有更少的副作用,CB 受体(CBR)在神经元和胶质细胞中都有表达。一种大麻素提取物(SativexTM)已被批准用于人类治疗,这意味着大麻的使用在许多国家可能会合法化,并且大麻素药理学提出了大麻素(天然或合成)的各种可能性,这些可能性都有可能被批准并用于治疗神经退行性疾病。