New treatments for neurodegenerative diseases: On the horizon?
Chronic neuroinflammation plays a critical role in the onset and progression of a broad range of neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease, and multiple sclerosis. CNS inflammation is mostly driven by activation of resident microglia, which normally acts as the first line of defense against injury and invading pathogens. However, activated microglia produce pro-inflammatory cytokines and other cytotoxic factors like prostaglandin E2 (PGE2) and reactive oxygen species that can damage adjacent neurons, further exacerbating tissue inflammation. Therapies that selectively target activated microglia would be valuable tools for treating neurodegenerative diseases.
A recent study by Santarsiero, et al. describes the discovery of novel compounds with impressive anti-neuroinflammatory properties. The authors synthesized a series of polyoxygenated diarylheptanoid compounds and tested their ability to reduce inflammatory mechanisms in a cell-based model of microglia activation. Though the newly synthesized compounds did not affect cell viability, they did effectively inhibit expression of proinflammatory cytokines IL-6 and TNF-a, and they also led to reduced production of nitric oxide and PGE2 as measured with an ELISA kit from Arbor Assays. Remarkably, the compounds demonstrated considerable anti-neuroinflammatory activity at nanomolar concentrations which are much lower than those observed with naturally occurring linear diarylheptanoids. These important studies may lead to future development of novel compounds for treating neurodegenerative diseases.
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