In a commentary recently published in the Journal of Alzheimer’s Disease, Ian Clark and Craig Atwood discussed some novel mechanisms and viewpoints related to the “cross-talk” between tumor necrosis factor (TNF) and endocrine dyscrasia, and how this might affect the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), stroke and traumatic brain disease.
Endocrine dyscrasia is an age-related dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis and is associated with dyotic signaling and the induction of neurodegenerative cascades within the brain.
These endocrine changes, and particularly, the elevation of gonadotropins concentrations and the loss of sex steroid signaling, have been recently linked to the development of Alzheimer’s disease (AD). Current evidence also indicates that in AD, the inﬂammation (and thus, the expression of pro-inflammatory cytokines) is most likely an early step that initiates the disease rather than a late step that minimizes the disease.
In the Journal of Alzheimer’s Disease commentary, Ian Clark and Craig Atwood suggest that both the loss of sex steroids/inhibins and the elevation of GnRH/gonadotropins with age-related endocrine dyscrasia, would serve to elevate TNF expression in the brain.
According to the authors, better understanding of these widespread functional links between the gonadotropins, sex steroids, and TNF may provide further insights into the pathogenesis of, and therapy for neurodegenerative diseases.
SOURCE: J Alzheimers Dis 2011, Sep 2. [Epub ahead of print]