Overview Of Glial Activation And Proinflammatory Biobioce

Association). While current research efforts have looked to determine how and why AD is caused, the pathogenesis of the disease in patients is

The topics include: Alzheimer’s disease and what provokes it, amyloid-beta proteins, synapses, synaptic pruning, neurons, cognitive and microglial cells. Alzheimer’s disease affects mostly individuals in their mid-60s and is “a type of dementia that causes problems with memory, thinking and behavior” (Alzheimer 's Association). The articles reflect the discovery of the Alzheimer’s disease affects the brain by the destruction of the connection of the brain cells which causes damage in neurons and accelerate cognitive decline, and occasionally call it the earliest stage. Amyloid-beta is a term that refers to the plaques made by the proteins which interferes and cause the loss of synapses also known as synaptic pruning is the loss of connections between neurons caused microglia, that according with The Campbell Biology In Focus textbook, “microglia are immune cells that protect against pathogens” (Campbell.) The authors of the research support “microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in Alzheimer’s disease.” (Taub, 2016)

Black has stated that genetic causes often involve the mutation of multiple genes and have identified at least five chromosomes: 1, 12, 14, 19, and 21 (Black, 2009, p. 1894). Four genetic loci have also been identified as contributing to AD, including the amyloid precursor gene, the presenilin 1 gene, the presenilin 2 gene, and the apolipoprotein E gene on chromosome 19. Though there is not enough conclusive research to directly link AD to environmental factors (such as toxins or head trauma) or personal health (diabetes, vascular disease, heart and stroke), these issues are known to contribute to the destruction of brain cells. Understanding the etiology of brain cell loss is relevant to understanding how to effectively prevent the loss of function in the brain. For example, preventing the formation of chemicals called free radicals with antioxidants can indirectly prevent AD. Other causes of brain cell loss include a neurotransmitter called glutamate and an accumulation of beta amyloid proteins. Therefore, although the cause of AD has been unidentifiable, many contributing factors have been observed.

“Alzheimer’s Disease (AD) is a type of dementia, which is affecting the population that develops in the brain and can lead to problems with memory, thinking and behavior”. The Amyloid Hypothesis claims that the build up of the beta-amyloid in the brain is a cause in the development of Alzheimer disease in patients. This plaque of the beta-amyloid and its cascade of events can be linked to the deterioration and negative effects of cognitive function of the brain over time. The beta-amyloid is described to be a “sticky” protein located in the brain therefore plaques or build up of the amyloid is common. These plaques in turn can block the brain cells from communicating with each other. Which then activates an immune system, that leads to inflammation

Nevertheless, both types of AD are recognised pathologically by the build-up of intracellular neurofibrillary tangles, extracellular amyloid plaques, and massive neuronal and synaptic loss (Carmo & Cuello, 2013). Neurofibrillary tangles are aggregates of hyper-phosphorylated tau protein and plaques are mostly insoluble deposits of β-amyloid, resulting from the cutting of the amyloid precursor protein (APP) (Farooqui & Farooqui, 2011). The discovery of mutations in the APP gene which cause familial AD lead to the articulation of the amyloid cascade hypothesis (ACH) (Hardy & Asllop, 1991). A large amount of evidence supports this view; however a number of findings are contrary to its proposal. As a result, Armstrong (2011) proposed a revision of the hypothesis, postulating that the main trigger for the development of the disease is the ageing of the brain and related wear and tear such as head trauma and stress; collectively referred to as the “allostatic load” (Carroll, 2002). Furthermore, a greater emphasis has now been placed on the role of small, soluble amyloid oligomers which seem to be the cause of early cell dysfunction in AD, rather than the large, insoluble amyloid fibrils. (Ferreira, Vieira & De Felice, 2007).

The Aβ deposition and diffused plaque formation lead to local microglial activation, cytokine release, reactive astrocytosis and a multi-protein inflammatory response (Eikelenboom

of Americans with AD will reach around 15 million by 2050. Neglecting to give a cure to this malady will have enormous effects on human enduring, as well as monetarily and socially (The Alzheimer's Project, 2009). Consequently, curing AD is of quick essentialness. A number of medications proposed to ease off or stop the malady are presently in clinical trials as far and wide as possible. The essential trials of AD – the infection changing medications, are hostile to amyloid medicines that are attempting to abate its movement

However, before this study was done no previous evidence was determined. At this time, correlation of the two genes had already been linked to Alzheimer’s disease but not brain atrophy. Gene ABCA7 has shown to influence amyloid plaque and neuronal cholesterol efflux. This study also found that higher blood expression of ABCA7 correlates not only to cortical atrophy but also poor memory, executive performance, and language. The gene MS4A6A is thought to be damaging to the brain because of the increasing number of microglia with pro-inflammatory

In the 1960 's, scientist found a relationship between cognitive decline and the number of plaques in the brain. In the 1970’s AD was documented as the most common type of dementia (Bright Focus Foundation, 2015). In 1984 another ground breaking discovery was made. In 1984 the Beta-Amyloid was discovered by George Glenner and Cai 'ne Wong (Alzheimer’s Association, 2015). In the 1990 's a few more discoveries were made, such as complex nerve cells, and genetics coincident, and AD susceptibility. However, the last decade has been crucial to AD discoveries and experiments. As technology is always improving, scientists are able to push their limits and experiment more.

Alzheimer’s disease (AD) is a neurological disorder affecting an estimated 36 million people worldwide [1]. Clinical manifestations commence with discrepancies in memory but inevitably progress to irreversible cognitive decline. A key neuropathological feature of AD is the accumulation of amyloid plaques in the parenchyma of the neocortex, amygdala and hippocampus [2] (Figure 1).

Amyloid beta (Aβ) is a short peptide contains 37 to 43 amino acids and is well known for its hypothesized role in causing pathogenesis of AD, since one of the main hallmarks of AD is the accumulation of fibrillogenic Aβ in the grey matter of the brain (14-15). Meanwhile, over 90% of AD patients have cerebral amyloid angiopathy (CAA) which is characterized by the deposition of Aβ in capillaries, arteries, and arterioles (16-17). CAA causes the degeneration of smooth muscle cells and leads haemorrhages (17).

While issues regarding concentration levels of Aβ, the types of Aβ and the mechanisms of its production remain poorly understood, some information has been found. For instance, the continuous overproduction of Aβ at dendrites or axons acts locally to reduce the number and plasticity of synapses (Parihar, 2010). Moreover, in mouse models for AD, the area of amyloid plaques is characterized by highly dysmorphic neurites and spine turnover causing a net loss of spines (Parihar, 2010). Such abnormalities in dendritic spines were found to develope before appearance of clinical symptoms in AD--likely due to cognitive reserve (Parihar, 2010). These characteristics could be caused by Aβ oligomers, which block long term potential (LTP) and directly induce long term depression (LTD), spinal loss and memory loss(Parihar, 2010). Likewise, in hippocampal culture, the soluble Aβ produced

The article titled: Microbiota Controls the Homeostasis of Glial Cells in the Gut Lamina Propria assessed the varying conditions in which Microbiota within the developing digestive tract can influence the process of network formation of the certain aspects of the enteric nervous system. The enteric nervous system (ENS) is the aspect of the digestive system endowed with its own nervous system (Bowen 2006). As far as the article is concerned, there were three important biological findings presented in the article concerning the ENS.

They support neighboring neurons and integrate the nervous communication unit in the form of tripartite synapse (Bosson et al., 2015). Astrocyte accumulation is the earliest pathological change in AD (Wyss-Coray et al., 2003). As a source of inflammatory factors in CNS, astrocytes may lead to neurotoxic damage by generating chronic self-sustaining inflammatory reactions (Griffin et al., 1998; Paradisi et al., 2004). However, a recent randomized clinical trial found inhibiting the inflammatory responses with anti-inflammatory drugs failed to improve cognitive function in elderly individuals with a family history of AD (Group et al., 2008), which implies inflammation may not be the only mechanism by which astrocytes contribute to the pathogenesis of AD. Soluble Aβ production in AD correlates well with the severity of memory/cognition impairment (Walsh and Selkoe, 2004). Aβ disrupts neuronal calcium homeostasis, induces oxidative stress (Mosconi et al., 2010), instigates tau hyperphosphorylation (Christensen et al., 2004; Seyb et al., 2006) and causes extensive synaptotoxicity and neurotoxicity, all of which contribute to the AD-like phenotypes observed in animal models (Matos et al., 2012; Shrivastava et al., 2013). A previous study has shown the expression of β-secretase was increased in astroglial cells in the brains of Tg2576 AD mice, which may facilitate the generation of Aβ in this transgenic mice

Apart from these classic hallmarks, increasing evidence has demonstrated uncontrolled glial activation and neuroinflammation in AD brain may contribute independently to neural dysfunction and cell death (Akiyama et al., 2000; Wyss-Coray and Mucke, 2002). Robust activation of microglia has been found in and around the area of amyloid plaques in the AD brain, and reactive astrocytes have been shown to form a halo surrounding the amyloid plaques (Itagaki et al., 1989; Ho et al., 2005). Additionally, numerous proinflammatory factors have been reported to be elevated in both patients with AD and transgenic animal models of AD (Griffin et al., 1989; Akiyama et al., 2000; Ruan et al., 2009). Whether alleviation of neuroinflammation will offer therapeutic benefit for AD remains unclear. Epidemiological studies show a possible association between suppression of inflammation and reduced risk for AD (in t’ Veld et al., 2001; Vlad et al., 2008). Therefore, drugs targeting neuroinflammation might provide benefits for the prevention and treatment of this devastating disease.