Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/ijms241411569
Keywords
neurodegeneration; microglia; inflammation; neuroprotection; trace amine-associated receptors type 1 (TAAR1); 3-iodothyronamine
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Microglial dysfunction is a hallmark and leading cause of common neurodegenerative diseases (NDDs). Inhibition of glial activation may be a therapeutic target. T1AM, an endogenous derivative of thyroid hormone, has shown potential neuroprotective effects, but its effects on microglial dysfunction remain unclear.
Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM's effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNF & alpha; or & beta;-amyloid peptide 25-35 (A & beta;25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediated inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNF & alpha;, NF-kB, MCP1, and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells turned out to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDDs.
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