Immune system in AD patients is severely affected by disease status [25]. Recent reports have been shown that the frequency and function of T and B cells in AD patients is decreased [9]. Several studies have been reported Fulvestrant research buy that the presence of proinflammatory circulating cytokines and lymphocyte subset distribution can be disturbed in AD [26]. Among the cellular components of the immune system, NK cells are thought to be key effectors owing to MHC-restricted cytotoxic activity against tumoural and viral targets

[27]. Although the immunobiology of NK cells in some neurodegenerative diseases such as multiple sclerosis (MS) is well studied, little is known regarding the precise role of NK cells in AD [28]. Thus, investigating about the precise role of these cells in immunopathogenesis of AD may open the new horizon for designing the new therapeutic methods. The first sign of NK cells involvement in AD immunopathogenesis appeared about two decades ago, when Krishnaraj [29] showed that THA (Tacrine), which was a potent drug in neurologic abnormalities such as AD, had a suppressive capacity in expansion and cytotoxic function of NK cells in AD patients compared to normal subjects. Thus, in this study, it is indirectly suggested that NK cells could be deleterious

factors in AD patients. Concomitantly, Araga et al. [30] showed that although the frequency of NK cells in AD patients and normal controls are similar, however, the functional potential of NK cells in AD patients was significantly lower https://www.selleckchem.com/products/LDE225(NVP-LDE225).html compared with normal controls. Other researchers also reported the decreased cytotoxic C-X-C chemokine receptor type 7 (CXCR-7) function of NK cells [26, 31]. Also intact frequency of NK cells was also reported in another study [9]. However, it seems that this controversial reports regarding the frequency and function of NK cells are in part due to the different methodology used by researchers and/or study on patients with different prognosis which may affect on results. Although it has been shown that NK cells have low degree of functional defects, there is evidence that indicates NK cells are potent responders to IL-2 [7, 32] or IFN-γ (29) stimulation in AD patients compared with healthy

controls. While some studies showed that NK cells are suppressed in AD patients, other investigators reported that their functional capacity is reversible following the stimulation by some factors such as IL-2. Thus, it seems that microenvironment milieu in CNS of AD patients is a critical factor that may modulate the NK cells function. On the other hand, it has been demonstrated that not only NK cells in AD patients are sensitive to stimulation by cytokines such as IL-2 or IFN-γ [27], but also they are resistant to immunosuppressive effects of some drugs such as cortisol [27, 33]. Solerte et al. [27] have suggested that overactivity of NK cells following cytokine mediated stimulation in AD patients is related to dysregulation of PKC (protein kinase C) expression in these patients.