Molecular chaperone α-crystallin prevents detrimental effects of neuroinflammation

Abstract

Silver nitrate administration stimulates immune activation, inflammation and deterioration in cell function. It is well established that hippocampal and cortical tissue are susceptible to degeneration in responses to insult such as oxidative stress or infection. This study was designed to investigate the prophylactic effect of alpha-crystallin, a major chaperone lens protein comprising of alpha-A and alpha-B subunits in inflammation induced mice. Mice were divided into three groups (n=6 in each), control, inflammation and alpha-crystallin treated. Our result shows that alpha-crystallin pretreatment effectively diminished systemic inflammation induced glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NFkappaB) expression in the mice neocortex, reversed elevated intracellular calcium levels, acetylcholine esterase activity and depletion of glucose. Furthermore it also significantly prevented nitric oxide (P<0.05) and lipid peroxide production in the plasma, liver, neocortex and hippocampus of the inflammation-induced mice. In order to demonstrate the direct *OH and nitric oxide radical scavenging ability of alpha-crystallin, an In vitro experiment using primary astrocyte culture subjected to lipopolysaccharide (LPS), a well-known inflammatory stimuli were also carried out. This study reiterates that alpha-crystallin therapy may serve as a potent pharmacological agent in neuroinflammation.

α-Crystallin Downregulates the Expression of TNF-α and iNOS by Activated Rat Retinal Microglia in vitro and in vivo

“…␣ -Crystallins can reduce the release of inflammation-induced cytokines, and it has been suggested that ␣ -crystallin has the potential to act as an anti-inflammatory agent in the neuroprotective process [9,10] . Protein misfolding and inclusion formation play important roles in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and multiple sclerosis.…”

“…As a class of heat shock protein, ␣ -crystallin exhibits chap- erone-like properties, including the ability to prevent the precipitation of denatured proteins and to increase cellular tolerance to stress [8] . Masilamoni et al [9,10] found that ␣ -crystallin pretreatment prevented TNF-␣ and NO production in lipopolysaccharide (LPS)-activated astrocytes in an inflammation-induced mouse model. This suggested a protective function by ␣ -crystallin in inflammation-triggered neurotoxicity.…”

Methionine sulfoxide reductase A: Structure, function and role in ocular pathology

“…Recent findings indicate that, in AMD, both MsrA and α-crystallin accumulate in the drusen, and the nature of their physical and molecular interactions under pathological conditions is not known. Further, α-crystallins are neuroprotective in multiple neurodegenerative diseases [71,[88][89][90][91][92] , and given the fact that oxidation of the methionine residues inhibits the chaperone function of crystallins, it is plausible that modulation (by overexpression) of the Msr activity may be beneficial in the treatment of these diseases. In addition, aging contributes to increased oxidation of methionine in proteins so that MsrA alone or in combination therapy could offer significant and long-term protection.…”

High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

“…Result from EBV Infection-One of the most debated autoantigens in MS is crystallin alpha-B (CRYAB), a heat shock protein with suppressive effects on (neuro)inflammation through chaperone-like activities (74). CRYAB binds a spectrum of unfolded or aggregated proteins, and it is highly expressed as a 24-subunit multimer in the eye lens, where it is a target antigen in patients with intraocular inflammation (75).…”