Rileychandler7937

Alzheimer disease is the dominant form of elderly dementia. Today all clinical trials that target β-amyloid have failed to indicate that β-amyloid may not be a causative agent in AD pathogenesis. Thus there is a need to search for alternative ways to treat AD patients. Neuronal store-operated calcium entry is a fine-tuning mechanism that regulates intracellular Ca2+ content. Recent evidence suggests that store-operated calcium channels may be targeted with pharmacological agents in order to prevent synapse loss, recover long-term potentiation and change behavior. Bak apoptosis Current mini-review discusses basic chemical structures that modulate intracellular calcium dysbalance via targeting store-operated calcium channels and their applicability as anti-AD pharmacological agents.

Recent evidence points to a possible link between the inflammatory modulatory protein S100B protein and the pathogenesis of Alzheimer's disease (AD).

To investigate the elevated levels of serum S100B protein among AD in a South Indian cohort and its correlation with severity of cognitive impairment.

A cross-sectional study was conducted with 100 AD patients and 100 age and sex matched healthy controls. Diagnosis of AD was made by a qualified neurologist using NINCDS ADRDA criteria. Measurement of serum S100B protein was performed using solid phase sandwich ELISA method in both cases and controls.

Significantly higher prevalence of elevated serum S100B protein 44(44%) (p<0.0001), hypertension 52(52%) (p=0.02), diabetes mellitus 58(58%) (p=0.002), thyroid dysfunction 28(28%) (p=0.009), positive CRP 46(46%) (p<0.0001) and lower mean Mini-Mental State Examination (MMSE) values 20.4±5.1 (p<0.0001) were seen in AD patients compared to controls. Elevated S100B protein levels were significantly associated with Clinical dementia rating (CDR) score 2(34%) (p=0,05) and score 3 (61.3%) (p=0.03) compared to normal levels. After multivariable logistic regression analysis positive C-Reactive Protein (odds 3.2; 95%CI 2.8-9.8)(p=0.001), elevated S100B protein (odds 9.0;95%CI2.2-35.8) and diabetes mellitus (odd1.2;95%CI1.0-4.9)(p<0.0001), were significantly associated with AD.

In our study, we established an independent association of elevated serum S100B protein levels with AD. Elevated S100B protein levels higher in CDR score 3.

In our study, we established an independent association of elevated serum S100B protein levels with AD. Elevated S100B protein levels higher in CDR score 3.Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder. Dysfunction of central cholinergic neurons, amyloid aggregation and deposition,oxidative stress,and biometal dyshomeostasis has been regarded as the major pathogenic mediators in this devastating disease. However, strategies derived from these hypotheses fail to slow down or stop the progression of AD, warranting a combination of therapies to target multiple etiological factors or examining alternative hypothesis. Store-operated calcium entry (SOCE) is the process by which depletion of calcium in the endoplasmic reticulum (ER) lumen causes an influx of calcium across plasmalemma. Accumulating evidence indicates that neuronal SOCE (nSOCE) is inhibited in family AD (FAD) and the inhibition of which causes instability of dendritic spines and enhances amyloidogenesis. Mutant Presenilin fails to function as an ER calcium leak channel and promotes degradation of stromal interaction molecules (STIM), ER calcium sensors; these effects may account for the repression of nSOCE in FAD. We have demonstrated that activation of autophagy degrades STIM proteins, resulting in a trimming effect on a dendritic arbor, under proteasome inhibition and endoplasmic reticulum stress, which are intimately connected with AD. Thus, we hypothesize that autophagy represses SOCE by degrading STIM proteins, leading to synapse loss in AD. This review article will highlight the roles of SOCE in AD neurodegeneration, the degradative mechanisms of STIM protein, and the therapeutic potential and associated challenge.The dysregulation of calcium signaling mechanisms in neurons has been considered a contributing factor to the pathogenesis evident in early-onset Alzheimer's Disease (AD). However, considerably less is known concerning the possible impairment of Ca2+ mobilization in resident immune cell microglia. This review considers findings which suggest that a prominent pathway for non-excitable microglial cells, store-operated calcium entry (SOCE), is altered in the sporadic form of AD. The patterns of Ca2+ mobilization are first discussed with platelet-activating factor (PAF) stimulation of SOCE in adult, fetal and immortalized cell-line, human microglia in the healthy brain. In all cases, PAF was found to induce a rapid transient depletion of Ca2+ from endoplasmic reticulum (ER) stores, followed by a sustained entry of Ca2+ (SOCE). A considerably attenuated duration of SOCE is observed with ATP stimulation of human microglia, suggested as due to agonist actions on differential subtype purinergic receptors. Microglia obtained from AD brain tissue, or microglia treated with full-length amyloid-β peptide (Aβ42), show significant reductions in the amplitude of SOCE relative to controls. In addition, AD brain and Aβ42-treated microglia exhibit decreased levels of Ca2+ release from ER stores compared to controls. Changes in properties of SOCE in microglia could lead to altered immune cell response and neurovascular unit dysfunction in the inflamed AD brain.

Beta amyloid (Aβ) peptide containing plaque aggregations in the brain are a hallmark of Alzheimer's Disease (AD). However, Aβ is produced by cell types outside of the brain suggesting that the peptide may serve a broad physiologic purpose.

Based upon our prior work documenting expression of amyloid β precursor protein (APP) in intestinal epithelium we hypothesized that salivary epithelium might also express APP and be a source of Aβ.

To begin testing this idea, we compared human age-matched control and AD salivary glands to C57BL/6 wild type, App

, and APP/PS1 mice.

Both male and female AD, App

, and APP/PS1 glands demonstrated robust APP and Aβ immunoreactivity. Female App

mice had significantly higher levels of pilocarpine stimulated Aβ 1-42 compared to both wild type and APP/PS1 mice. No differences in male salivary Aβ levels were detected. No significant differences in total pilocarpine stimulated saliva volumes were observed in any group. Both male and female App

but not APP/PS1 mice demonstrated significant differences in oral microbiome phylum and genus abundance compared to wild type mice.