The phospho (P)-tau levels at the AT8 phosphorylation sites are higher in the allergic animals than those in the controls, both in the hippocampus (< 0.01) (A) and in the parietal cortex (< 0.01) (B). of both immunoglobulin (Ig) G and IgE with a common distribution. Allergy was also found to increase phosphorylation of tau protein in the brain. The present data support the notion that allergy-dependent chronic peripheral inflammation modifies the brain inflammatory status, and influences phosphorylation of an AD-related protein, indicating that allergy may be yet another factor to be considered for the development and/or progression of neurodegenerative diseases such as AD. Keywords: immunoglobulin, neuroinflammation, tau-phosphorylation, Alzheimer's disease Introduction Systemic inflammation has been shown to worsen the progress of Alzheimer's disease (AD) [1]. Elevated plasma levels of inflammatory proteins have been detected before clinical onset in patients with AD and moderate cognitive impairment (MCI) [2, 3], suggesting that chronic inflammation may be involved in the initiation and progress of the disease. AD is usually a neurodegenerative disorder characterized by progressive dementia with devastating effects for the patients and their families. The cause of the sporadic form of the disease accounting for more than 95% of the cases is usually unknown while available treatments are purely symptomatic. Therefore, it would be of great value to find treatment strategies aiming at the etiopathogenesis of Salinomycin sodium salt AD. The theory of immunopathogenesis of AD has obvious therapeutic implications. Firstly, retrospective studies have shown decreased AD prevalence and progression rate in elderly patients with history of long-term anti-inflammatory therapy [4]. Second of all, immunomodulatory strategies in animal models have been shown to result in encouraging effects on AD-related behavioural and pathological features [5C8]. Thus, the notion that inflammation represented in the periphery gives rise to central manifestations related to the pathophysiology in AD, could represent an opportunity to modulate a factor involved in disease pathogenesis. Despite the existing knowledge regarding the neuropathology of the disease, the cause of Mouse monoclonal to SNAI2 AD is not known. The neuropathological hallmarks of AD Salinomycin sodium salt are the extracellular amyloid deposits, comprised mainly of -amyloid (A) peptide, and the intracellular neurofibrillary Salinomycin sodium salt tangles (NFTs), consisting of hyperphosphorylated tau protein [9]. Reduced synaptic density and neuronal loss Salinomycin sodium salt are also part of the neuropathology in the AD brain. The extent of NFTs primarily found in brain regions that are critical for memory [10] seems to better correlate with the severity of dementia in humans than the amyloid plaques [10C12]. It has been hypothesized that NFTs are responsible for impairing synaptic function, leading to cognitive malfunction [13]. The level of tau-phosphorylation is usually regulated dynamically by several kinases and phosphatases. Indeed, analysis of AD brain tissue showed that protein kinases such as glycogen synthase kinase 3 (GSK3), P25/Cyclin-dependent kinase 5 (Cdk5), as well as mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated MAP kinase (ERK) ? pathway, the c-Jun-N-terminal kinase (JNK) pathway, and the p38 pathway, are increased in expression and/or activity [14]. Decreased activity is usually observed for protein phosphatases (PPs) such as PP1, PP2A and PP5 [15]. Therefore, an imbalance between the activities of kinases and phosphatases may cause tau-hyperphosphorylation, which may be related to clinical symptoms encountered in AD. A large body of evidence suggests that inflammatory processes in the brain have an important, but yet not obvious role in the initiation and/or progression of AD [16, 17]. The inflammatory component in AD consists of microglial activation followed by astroglial proliferation, with the production of several inflammatory proteins, such as pro-inflammatory cytokines, chemokines, match factors and acute phase reactants. An increased expression of pro-inflammatory cytokines such as interleukin (IL)-1 has been found in the human AD brain [18], and transgenic mice with AD-pathology have increased expression of IL-1 and IL-6 in the brain [19, 20]. Decreased levels of the endogenous IL-1 receptor antagonist (IL-1ra) in cerebrospinal fluid (CSF) from AD patients Salinomycin sodium salt may show an imbalance between IL-1 and IL-1ra in the AD brain [21], whereas the increased levels of the soluble IL-1 receptor type II (sIL-1RII) [22] may suggest an attempt to balance the inflammation. Allergy is usually a highly prevalent peripherally manifested chronic inflammatory condition affecting around.
The phospho (P)-tau levels at the AT8 phosphorylation sites are higher in the allergic animals than those in the controls, both in the hippocampus (< 0