RESEARCH NEWS

EXPERIMENTAL MODELS

Drug's effect on Alzheimer's may depend on severity of disease

andMutation stops worms from getting drunk

Laura Cristina Castrillón ValenciaMedicine student

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Cells as Experimental Models

In the investigation, specially medicalresearch is used the scientific method, whichis based in the evidence; work with humansin a laboratory or in an experimentaltreatment is very expensive and unethical,for the possible risks that have anexperimental process, for that reason severaldifferent kind of cells and organisms are usedfor experimental trials, it is possible becausealthough phenotypically organisms aredifferent, the unit of the live, the cell, hascharacteristics and the fundamentalproperties, which have been conservedduring evolution, it allows perform changeswith one type of cell and apply the similarprocess to other cells.

In this presentation you could knowtwo different examples oforganisms as experimental modelsused in investigation: A transgenicmouse studied in an Alzheimer ´sdisease and a mutant worms thatdon’t get intoxicated by alcohol,which could be lead to new drugsto treat the symptoms of peoplegoing through alcohol withdrawal.

Drug's effect on Alzheimer's may depend on severity of

disease

¿What is about this new?

Researchers at theUniversity of Illinois atChicago College ofMedicine work in atransgenic mouse, whichcurrently is the bestanimal model of theAlzheimer´s disease (AD),because it has a humangene that confers onpeople a 15-fold elevatedrisk of developing AD.

They are doing testswith a cancer drug,bexarotene, which inlate-stage Alzheimer´sreduces 40 percentlevels of neurotoxicprotein amiloyd-beta,which is increased in

AD.

Alzheimer's disease

It is the most common form of dementia in older people.

It affects parts of the brain that control thought, memory and language

Dementia

Symptoms caused by disorders that affect the brain

It is the progressive loss of cognitive functions, but not a specific disease

Drug's effect on Alzheimer's may depend on severity of disease

One of the principal characteristics ofthe Alzheimer’s diseases is theaccumulation dense plaques in thebrain composed of clumps of amyloid-beta.

Everybody produce this protein in the brain, but there are a mechanism responsible to clean this clumps, it is for ApoE , which is a protein mutated in patients with AD.

Drug's effect on Alzheimer's may depend on severity of disease

“ApoE4 is the greatest genetic risk factor for Alzheimer´s disease”,

said LaDu, who is one of the researcher.

Alzheimer treatment pretends eliminate clumps of amyloid-beta, for that reason the investigations

are focus in this challenge.

Bexarotene is a cancer drug used for skin cancer, but also it reduces

the clumps of amyloid-beta.

Drug's effect on Alzheimer's may depend on severity of disease

I think is very important have different points of view about the same problem investigation,

because diseases like Alzheimer, which is unknown the real cause and just know some

characteristics of the diseases need advance in the evidence about the hypothesis raised, and in this case the use of cells as experimental models

is crucial to reduce the experimenter bias and propose solutions for diseases that are increase

exponentially.

Drug's effect on Alzheimer's may depend on severity of disease

PERSONAL OPINION

Mutation stops worms from getting drunk

Mutant worms have been generated by researchers at The University of Texas atAustin, who pretend create a new drug to treat the symptoms of people goingthrough alcohol withdrawal.

Scientists insert a modified human alcohol target into the worms, which give them the first example of

altering a human alcohol target to prevent intoxication in an animal.

Caenorhabditis elegans, was the modelintoxication used in the study.

Mutation stops worms from getting drunk

- Alcohol causes the worms to slow their crawling with lesswriggling from side to side.

- The intoxicated worms also stop laying eggs, which build upin their bodies and can be easily counted.

But these worms are not as ideal for studying the other areas of alcohol addiction, for that reason mice cold be an excellent model.

What happen with worms´s modification?

Mutation stops worms from getting drunk

It is any neuronal molecule that binds

alcohol

The effects of alcohol on the body are complex and have many targets across

the brain

One important aspect of this modified alcohol target: a

neuronal channel called the BK channel, which has several

functions

The mutation only affects its response to alcohol

Alcohol target

Mutation stops worms from getting drunk

Typically regulates many important functions including activity of neurons, blood vessels, the

respiratory tract and bladder.

The voltage- and Ca(2+)-activated K(+) (BK) channels.

It is very important in the neurotransmitter´s regulation and

neural excitability

Structurally are homologous to voltage and ligand-gated K(+)

channels, having a voltage sensor and pore as the membrane-spanning domain and a cytosolic domain containing metal binding sites

BK channels also contribute to the behavioral effects of ethanol in the

worm C. elegans

BK channel

Mutation stops worms from getting drunk

PERSONAL OPINION

For the human, the self-will is the most complicated psychological aspects of dealing, and currently molecular

biology and genetic are the future of medicine, according to these ideas, I think this investigation is a perfect example of the molecular and genetic application: prevent problems in

alcohol abuse disorders using modified human alcohol target.

MEDICAL UTILITY

Currently in the word 26 million people suffer from some form of dementia. Predictions says that the number could be double

every 20 years until 81 million in 2040.

Clinical trials are used in medicine tostudy and analyze the behavior ofsome treatment with theobjective to improve alternatives forsome diseases.

Alzheimer is the most common formof dementia and there are severalinvestigation focus in this disease.

MEDICAL UTILITY

MEDICAL UTILITY

The results of thisinvestigation couldpotentially be usedto treat alcoholics,since it wouldcounteract theintoxicating andpotentiallyaddicting effects ofthe alcohol.

MEDICAL UTILITY

These modified mice would allow scientists to

investigate whether this particular alcohol target also affects tolerance,

craving and other symptoms relevant to

humans.

BIBLIOGRAPHY

1. Case Western Reserve University. Hallan forma de revertir los efectos del Alzheimer en el cerebro. [ online ].BBC mundo, 2012. <Avaible from:http://www.bbc.co.uk/mundo/noticias/2012/02/120210_alzheimer_farmaco_placas_men.shtml> [Retrieved July 18, 2014]

2. COOPER, GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. CellsAs Experimental Models. Available from: http://www.ncbi.nlm.nih.gov/books/NBK9917/

3. MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 2. ed. Medellín: UPB. Fac. de Medicina, 2012. 10-12p.

4. University of Illinois at Chicago. Drug's effect on Alzheimer's may depend on severity of disease. [ online ].ScienceDaily, 2014. . <Avaible on: www.sciencedaily.com/releases/2014/07/140716123450.htm> [ RetrievedJuly 16, 2014]

5. University of Illinois at Chicago. Mutation stops worms from getting drunk. [ online ]. ScienceDaily, 2014. .<Avaible from: www.sciencedaily.com/releases/2014/07/140715214303.htm> [ Retrieved July 16, 2014]

THANKS