Abstract
Parkinson’s disease is a neurodegenerative disorder, the motor symptoms of which are associated classically with Lewy body formation and nigrostriatal degeneration. Neuroinflammation has been implicated in the progression of this disease, by which microglia become chronically activated in response to α-synuclein pathology and dying neurons, thereby acquiring dishomeostatic phenotypes that are cytotoxic and can cause further neuronal death. Microglia have a functional endocannabinoid signaling system, expressing the cannabinoid receptors in addition to being capable of synthesizing and degrading endocannabinoids. Alterations in the cannabinoid system—particularly an upregulation in the immunomodulatory CB2 receptor—have been demonstrated to be related to the microglial activation state and hence the microglial phenotype. This paper will review studies that examine the relationship between the cannabinoid system and microglial activation, and how this association could be manipulated for therapeutic benefit in Parkinson’s disease.
Highlights
Microglia are the resident mononuclear phagocytes of the central nervous system (CNS) and are found ubiquitously throughout the brain and spinal cord
In 2010 yet more definitive evidence was provided by Ginhoux et al [40], who used in vivo fate mapping in mice to show that adult microglia are derived from primitive macrophages, which arise from the embryonic yolk sac during development, and enter the brain rudiment via the circulatory system
Microglia play a crucial role in the uninjured brain, carrying out homeostatic maintenance and constantly monitoring their local microenvironment for indications of danger
Summary
Microglia are the resident mononuclear phagocytes of the central nervous system (CNS) and are found ubiquitously throughout the brain and spinal cord. As part of the innate immune system, microglia act as sentinels, constantly scouring the environment of the CNS for the first signs of danger, such as pathogens or tissue damage [3,4,5,6]. Detection of such signals initiates a cascade of responses that aim to resolve the injury. If chronic microglial activation persists, it can have a detrimental effect on the preservation of homeostasis in the CNS and can contribute to disease, as is the case with age-related neurodegenerative disorders such as Parkinson’s disease (PD).
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