Inflammatory Mediators as Biomarkers in Brain Disorders

Abstract

Abstract-Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases.

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

“…A" fibrils consist of 5-6 strands of protofibrils bundled in parallel. The aggregation of A" peptides is fundamentally associated with its neurotoxic effects and has been found to trigger oxidative stress and inflammation (Walsh et al 1999;Chauhan and Chauhan 2006;Pimplikar 2009;Nuzzo et al 2014). In vitro and in vivo studies have shown that soluble globular A" oligomers consisting of 3 to 24 monomers (A" derived diffusion ligand (ADDL)) and curvilinear, beaded oligomers measuring 3-6 nm in diameter and 200 nm in length (protofibrils) formed during the early phases of the A" aggregation process are the potentially toxic A" species, rather than unstructured monomers or the aggregated end-product, fibrils (Walsh et al 1999;Klein 2002).…”

“…Aside from the two major known neuropathological AD hallmarks, senile plaques and neurofibrillary tangles, a number of pathological abnormalities, including microglial activation and inflammatory processes, are found in AD brains (Nuzzo et al 2014;Zhou et al 2014;Kim et al 2008). Chronic inflammatory reactions are also common symptoms among age-related neurodegenerative disorders.…”

“…Inflammation mediator molecules such as cytokines, chemokines, macrophages, prostaglandins, coagulation factors, and reactive oxygen species have been detected in the AD brain . Genetic studies have shown that polymorphisms in some genes that encode for inflammatory interleukins 1' and 1" enhance the risk of AD Nuzzo et al 2014). These findings suggest chronic inflammation may play an important role in AD pathogenesis.…”

“…Accumulating evidence indicate that the misfolding and aggregation of the amyloid-" (A") peptide, which is a fragment of the APP protein, is a central pathogenic event associated with AD development (Suh 1997;Hardy and Selkoe 2002;Haass et al 1993). Several reports have also shown that reactive oxygen and nitrogen species, metal ions, and inflammation can be triggers for AD (Nuzzo et al 2014;Cuajungco et al 2000;Chauhan and Chauhan 2006;Gu et al 2008).…”

Exploring the Potential Role of Inflammation as an Etiological Process in ASD

“…Several studies report that depression (Dowlati et al 2010;Lotrich et al 2007Lotrich et al , 2009, bipolar disorder (Goldstein et al 2009), neurodegenerative diseases (Nuzzo et al 2014), and schizophrenia (Potvin et al 2008) are associated with inflammation in some capacity. Recently, studies utilizing child participants have begun to examine inflammation as one process which is trans-etiological in nature (Mitchell and Goldstein 2014;Rossignol and Frye 2014).…”