José Ángel Pagán López November 13, 2009 Biol 3095-142

-Amyloid Oxidative Stress and free radical theory in Alzheimer Disease Brain

Table of Contents

I. Abstract………………………………………………………………….…………..1

II. Introduction………………………………………………………………………1-2

III. Body

a. Alzheimer Disease………………………………………………………2-3

b. Oxidative stress……………………………………………………………3

c. Free radical theory……………………………………………………...….4

d. Amyloid……………………………………………………………….4

IV. Conclusion………………………………………………………………………4-5

V. Cited References…………………………………………………………………...5

Abstract

The discovery of the AD had made an eminent challenge in finding a probable cure for

this dementia. The mayor outcome of this disease is the myloid proteins. These proteins

increase with the rate of age. Radical theory is present in this disease, specifically in amyloid

proteins, produced by oxidative stress. With a lot of factors contributing to AD like: aging,

production, fibrillization, and others there’s no available cure to the disease.

Introduction

The case presented by the German physician Alois Alzheimer, of a woman with 51 years,

that presented a severe remembrance, behavior, and language complications, marked the

discovering of the disease. After that the woman died, the autopsy revealed a shrunken brain and

abnormalities in brain cells1. This disease is Degenerative and terminal and the most common

1 http://www.helpguide.org/elder/alzheimers_disease_symptoms_stages.htm

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dementia that affects 26 millions of worldwide (Alzheimer Association 2008). This dementia

doesn’t have a cure and has different cognitive variations in the patients like: psychological

symptoms, behavior, functioning, and the impact of the caregivers, making the possible solutions

difficult to find2.

A mayor factor contributing to the disease is the oxidative stress that is the empowerment

of the antioxidant defense structure by the oxidative system. This stress is produced by free

radicals. Chauhan states that: “Oxidative stress plays an important role in neuronal degeneration

in AD. Soluble , fibrils, NFT, and mitochondrial abnormalities increase neurological

disorders. The free radicals that produce this disorder are the (ROS) reactive oxygen atoms,

showing enlarged levels of lipid peroxidation.” (Chauhan 2006).

Alzheimer Disease

As discussed, one of the mayor issues of the disease damages, consist in proteins. The

protein production increases with age, but along with AD, the proteins will have larger damage.

Also senile plaques, neurofibrillary tangles are present in the area damage. In the cores of the

plaques are located the Amyloid B proteins, which increases in the same rate as the (NFT). The

main developers of the Alzheimer disease are the: Aging, fibrilization, production, NFT

pathology. The figure.1: preset the mechanism of AD. The part (A) present: the balance of the

Reactive Oxygen Species (ROS) and the method of defense. In part (B): factor that induce AD

are more present than the ROS defense. (Chauhan 2006).

2 http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp

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Fig.1: Mechanism of AD (Chauhan 2006),

Oxidative Stress

The brain is the most aerobical organ in the body. It uses 20% of the oxygen of the

organism. In other hand the brain is rich in polyunsaturated fatty-acid, which enclose more

chances to oxidize. The sources of the brain oxidation are the metals and mitochondrial factors.

An overload in transition metals like zinc, copper and iron are seen in hippocampus, neocortex,

and olfactory bulb in patients of AD (Moreira 2008). The mitochondrion plays a crucial role in

the development of the oxidative stress. The fabrication of energy in ATP is also along with the

formation of the ROS as product of the oxidative phosphorilation. Next to the ages the ROS

increases making the chances of AD more critical. A review by (Alliev 2008) shows

deposition with mitochondrial abnormalities in the vascular walls of an overexpressing ABPP

transgenic mouse. Furthermore, a gene expression profile was carried out in an ABPP transgenic

mouse model in order to establish which genes may be critical for cellular changes in AD

progression. In addition, (Aliev 2008) demonstrated a decrease in mitochondrial membrane

potential and a reduction in ATP levels in neurons of an ABPP transgenic mouse model when

compared to littermate non-transgenic mice.

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Free Radical Theory

Most radicals that participate in the oxidative stress are the (ROS), they are: nitrogen and

oxygen molecules with unpaired electron, these are unstable and reactive. They search and grab

other electrons from biomolecules making the molecule a free radical to, creating a domino

effect. Some of the molecules that are affected are the lipids, the nucleic acids, and proteins.

They destruct the transport, the enzymatic activity, the fluidity and cross-linking. Excessively

stress result in cell death. A review of (Moreira 2008) clarifies that morphometry of electron

micrographs demonstrated mitochondrion abnormalities closely associated with AD.

Aß -Amyloid

The Beta Amyloid, is a peptide of 39-42 aminoacids. Two mayor sites have activity

towards oxidation, histidine and tyrosine. In mentioned sites they chelae transition metals ions.

The other active site is the methionine, it reduces metals to low valency forms. Studies by

(Kontush 2001) observed that copper had efficient catalysis oxidation than other metals. These

ions are extremely dynamic oxidants and they can catalyze further oxidation of biomolecules.

For instance, they produce highly reactive hydroxyl radicals from hydrogen peroxide, an

important by-product of mitochondrial electron transport. Phosphorilating the microtubulin-

binding has a role in the function organization of the neuron, in axonal morphology, polarity and

growth.

Conclusion

With the oxidative stress playing an important role in the progression of AD and with the

mitochondrial damage, it can be found a way of delay the process of oxidation. There must be a

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path to synthetize a protein that has more affinity to transition metal ions, in a way that the

amyloids will have a balance of production with the ROS, preventing the progression of the AD.

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