21 November 2016

Alzheimer's disease and age-related macular degeneration

Age-related blindness was associated with Alzheimer's type protein

Denis Strigun, Naked Science

British scientists have discovered that mutations of the MAP-2 protein associated with Alzheimer's disease can lead to age-related macular degeneration. The results are presented in the journal Experimental Eye Research – Taylor-Walker et al., The Alzheimer's-related amyloid beta peptide is internalized by R28 neuroretinal cells and disrupts the microtubule associated protein 2 (MAP-2).

Macular degeneration is a group of irreversible diseases in which the retina of the eye is affected due to a violation of the blood supply. Macular degeneration is considered the main cause of blindness in the elderly, but the mechanisms of its development have not been sufficiently studied. It is known that the risk factors in this case are race and heredity. Thus, previous studies have shown that age-related visual dysfunction is more common in Europeans and is associated with a mutation of the SERPING1 (C1NH) gene encoding a C1 inhibitor.

A number of studies also indicate the connection of macular degeneration with the accumulation of beta-amyloids in the retina of the eye – peptides that supposedly provoke Alzheimer's disease. In a new paper, scientists from the University of Southampton analyzed molecular changes in macular degeneration in the cells of the neuroepithelium (R28) of the retina of mice. To do this, the cells were treated with human beta-amyloids or a control substance, after which, eight days later, a histological examination was performed.

The results showed that protofibrils appeared in the retina of individuals treated with beta-amyloids after 60-90 minutes. After 24 and 48 hours, the authors observed a sharp spread of the neurofibrillary tangles themselves. Analysis of genetic expression allowed them to identify markers of the anomaly: mutations of protein kinase C-alpha, calbindin, as well as protein associated with microtubules (MAP-2). In addition, scientists have demonstrated for the first time that R28 cells are expressed by calretinin.

Preliminary mechanism of the effect of beta-amyloids on the neuron
(from an article in Experimental Eye Research)

After that, beta-amyloids were injected into healthy mice. Eight days later, they also showed signs of developing the disease. The researchers note that the high rate at which peptides spread in the retina of animals was a surprise. The data obtained clarify the role of beta-amyloids in age-related macular degeneration. The next step will be to identify the ways in which these proteins penetrate into the retina of the eye, and to develop measures aimed at preventing their biosynthesis.

MAP-2 is a recombinant human protein that controls microtubules in cells. It is in the same group with tau protein (MAPT), often found in neurons of the central nervous system (CNS). In Alzheimer's disease, tau protein stops stabilizing microtubules and hyperphospholates, resulting in neurofibrillary tangles - accumulations of insoluble protein – forming in neurons. MAPT mutations can occur as a consequence of traumatic brain injury or contact with heavy metals, for example, mercury.

Portal "Eternal youth" http://vechnayamolodost.ru  21.11.2016

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