Sulforaphane Attenuates Aß Oligomers Mediated Decrease in Phagocytic Activity of Microglial Cells.

Microglia are the brain mononuclear phagocytes which plays a key role in neurodegenerative diseases, like Alzheimer's. Till date, microglia have been explored mostly for their neuro-inflammatory functions. Recent studies have shifted their focus towards less explored functions which involve non-autonomous clearance of protein aggregates. However, these functions are significantly affected by aging and neurodegeneration. In Alzheimer's disease (AD), microglia have been reported to clear amyloid beta (Aß) deposits via phagocytosis or release various pro-inflammatory cytokines. Whether microglia could be beneficial or detrimental to the brain, it all depends upon the type and strength of stimulus. So, if their beneficial properties could be selectively harnessed without activating pro-inflammatory response, a potential therapeutic strategy could be developed to check the formation of protein aggregates like Aß. In the present study, we have checked the effect of toxic amyloid beta oligomers (Aßo) on the microglial phagocytic activity. Our findings revealed that at lower concentrations, Aßo are not toxic to the cells and they can survive even with longer exposures but with decreased phagocytic activity. However, at higher concentrations Aßo become toxic and resulted in modulation of various genes which regulates microglial phagocytic activity. Sulforaphane (SFN) treatment has shown to induce the phagocytic activity of Aßo treated microglial cells. In addition, low dose Aßo and SFN treatment have not shown modulation in the levels of pro-inflammatory mediators of microglia. Taken together, these findings suggest that SFN treatment may ameliorate the Aßo mediated decrease in microglial phagocytic activity.

Evaluating the Role of Microglial Cells in Clearance of Aß from Alzheimer's Brain.

Ever increasing incidence of Alzheimer's diseases (AD) has been reported all over the globe, and practically no drug is currently available for its treatment. In the past 15 years, not a single drug came out of clinical trials. The researchers have yet to discover a drug that could specifically target AD; in fact, the drugs that are about to launch in the global market either belong to natural compounds or are already approved drugs targeting other diseases. So, we need to shift our focus on finding novel targets which are more specific and could either detect or inhibit the disease progression at a very early stage. Microglia are the only resident innate immune cells of the brain that are originated from erythromyeloid progenitors. They migrate to the brain during early embryonic development, although their number is less (∼5 to 10%), but they could act as guardians of the brain. It has been shown that the extracellular deposits of Aß are continuously phagocytosed by microglia in healthy individuals, but this ability would decrease with age and lead to development of AD. In this review, we have explored the possibility of whether microglial cells could be utilized as an early predictor of the AD progression. Here, we discuss the innate immune response of microglial cells, the factors affecting microglia response, microglial receptors to which Aß could bind, and microglial phenotype markers. Last, we conclude with a list of available AD therapeutics along with their mechanism.