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Alzheimer's Disease

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Madison Darmofal

on 25 November 2013

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Transcript of Alzheimer's Disease

Current Direction of Research
Find correlation between diabetes and Alzheimer's because of insulin pathway
Researchers trying to focus diabetic drugs on targeting brain cells
Background Information
50-80% of dementia cases
Progressive disease that worsens with time
It is not a normal part of aging, although it is associated most often with people 65 years and older
Difficulty remembering new information, disorientation, changes in mood
Destruction of nerve cells causes memory failure
Trouble understanding visual images and spatial relationships
Problems with speaking or
Faulty Mechanism
Beta Amyloid Peptide
The enzymes that cut Amyloid Precursor Protein determines whether or not APP becomes harmful
These enzymes are alpha-secretase, beta-secretase, and gamma-secretase
Alpha secretase cuts APP molecule to create sAPPα, which promotes neuron growth and survival.
The remaining APP fragment is cut by gamma-secretase at the end of the segment. This does not cause any harm to the brain
Beta-secretase cuts APP molecule at one end of the beta-amyloid peptide
Gamma-secretase cuts other end of beta - amyloid peptide
Resulting fragment released into the space outside the neuron is sAPPβ.
sAPPβ is sticky, small and soluble and two to twelve clump together to form oligomers (some which are cleared from the brain). If they are not, the oligomers continue to grow and when proteins and other cellular materials are added, it becomes insoluble and becomes plaque
Correct Mechanism
Alzheimer's Disease
by Kathryn Achuck, Madison Darmofal and Emily Teichman

Amyloid Beta Peptide Oligomers
Induce neuronal insulin resistance by activating kinase JNK
Phosphorylation of IRS-1 (insulin receptor substrate -1) with serine leads to insulin resistance
Phosphorylation of IRS-1 with tyrosine is essential to insulin stimulated signaling pathway
Insulin helps block effects of Amyloid Beta Peptide Oligomers
Modified Tau Protein can also lead to alzheimers when they separate from the microtubules and form tangles, which block communication and kills the neurons.
Neurons release neurotransmitters, which travel from one neuron to another through a synapses
They move from a presynaptic cells, through the synapse, then to postsynaptic cells

Each neurotransmitter has a specific receptor on the other neuron and they carry signals that can either stimulate or inhibit the brain
The postsynaptic cells contain many types of receptors, such as ligand gated channels and G Protein coupled receptors
Alzheimer's disease fact sheet. (2012, September). Retrieved from http://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet

Alz.org: Alzheimer's association. (2013, November 21). Retrieved from http://www.alz.org

Bomfim, T. R., & Forny-Germano, L. (2012). An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by alzheimer’s disease–associated aβ oligomers. The Journal of Clinical Investigation, 122(4), 1339-1353. doi: 10.1172/JCI57256

Jannis, S. (Director) (n.d.). Inside the brain: Unraveling the mystery of alzheimer's disease [Web]. Retrieved from http://www.nia.nih.gov/alzheimers/alzheimers-disease-video

Trommsdorff, M., Borg, J. P., Margolis, B., & Herz, J. (1998). Interaction of cytosolic adaptor proteins with neuronal apolipoprotein e receptors and the amyloid precursor protein. The Journal of Biological Chemistry, (273), 33556-33560. doi: 10.1074/jbc.273.50.33556

Amyloid precursor protein (APP) is a ligand for the low density lipoprotein (LDL) receptor-related protein (LRP), an abundant neuronal surface receptor that has been genetically linked to Alzheimer’s disease.
postsynaptic receptor
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