Modulation of the sigma-1 receptor-IRE1 Pathway Is Beneficial in Preclinical Models of Inflammation and Sepsis
Abstract: “Chronic low-grade inflammation has been observed in major depression and other major psychiatric disorders and has been implicated in metabolic changes that are commonly associated with these disorders. This raises the possibility that the effects of dysfunctional metabolism may facilitate changes in neuronal structure and function which contribute to neuroprogression. Such changes may have implications for the progress from major depression to dementia in the elderly patient. The purpose of this review is to examine the contribution of inflammation and hypercortisolaemia, which are frequently associated with major depression, to neurodegeneration and how they detrimentally impact on brain energy metabolism. A key factor in these adverse events is insulin insensitivity caused by pro-inflammatory cytokines in association with desensitised glucocorticoid receptors. Identifying the possible metabolic changes initiated by inflammation opens new targets to ameliorate the adverse metabolic changes. This has resulted in the identification of dietary and drug targets which are of interest in the development of a new generation of psychotropic drugs.”
Leonard BE and Wegener G: Inflammation, insulin resistance and neuroprogression in depression. Acta Neuropsychiatr.32(1): 1-9 (2020).
Abstract: “Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain-skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis.”
Martins AM, Ascenso A, Ribeiro HM, Marto J: The Brain-Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System. Cells 2020 Mar 26;9(4). pii: E796. doi: 10.3390/cells9040796.
“Patients with idiopathic smell loss constitute an at-risk population for the development of Parkinson’s disease (PD). The study aimed to follow up a large number of patients with idiopathic smell and/or taste loss to define the incidence of PD in this population and, further, to assess characteristics of both olfactory and gustatory function and their possible association with PD development….”
Haehner A, Masala C, Walter S, Reichmann H and Hummel T: Incidence of Parkinson’s disease in a large patient cohort with idiopathic smell and taste loss. J. Neurology 266: 339-345 (2019).