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Lecture 22

PSYC 211 Lecture 22: PSYC211 November 29th

18 Pages

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PSYC 211
Jonathan Britt

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th November 29 Degenerative disorders There are many different kinds of neurodegenerative disease, such as prion diseases, Alzheimer's, Parkinson's, Huntington's, and ALS. Some of these conditions injure particular kinds of cells, others are more widespread. Degeneration is typically the result of apoptosis, which is triggered by collections (aggregates) of misfolded proteins that disrupt normal cellular function. Transmissible spongiform encephalopathy Contagious brain disease, such as mad cow and Creutzfeldt-Jacob disease, whose degenerative process gives the brain a sponge-like appearance Caused by accumulation of misfolded prion protein Spongiform means that when they die their brain resembles a sponge Their brain has holes in it due to neurons that are not there anymore Prion Protein that can exist in two forms that differ only in their three-dimensional shape The prion protein is at risk of being misfolded When a misfolded protein bumps into another well-folded one, it can cause this one to also become misfolded This creates clumps of misfolded proteins that all bind together Accumulation of misfolded prion protein is responsible for transmissible spongiform encephalopathies However, they are not the most prominent of the degenerative disorders Sporadic disease (another word for idiopathic diseases) Disease that is not obviously caused by heredity or an infectious agent Has an unknown cause Prion protein diseases can be genetic or sporadicand both forms can be transmitted to others by means of a simple misfolded prion protein But prion proteins often fall under the sporadic category Can be transmitted when an individual eats the neural tissue of another individual This cannot be prevented by cooking the neural tissue So once there is an outbreak, it becomes very dangerous Misfolded proteins often encourage more misfolding to occur. Thus, most neurodegenerative diseases can easily spread from neuron to neuron and from brain to brain. Bottom panel: anytime regular prion proteins was made in the cell, it would immediately be degraded even if the protein was well folded Dementia Loss of cognitive abilities such as memory, perception, verbal ability, and judgment that is caused by an organic brain disorder. Common causes are multiple strokes and Alzheimer's disease Alzheimers is a form of dementia Dementia is typically seen in old age Blanket term for several different types of degenerative disorders Alzheimer's disease Degenerative brain disorder typically caused by misfolded b-amyloid protein Clump together in the brain and causes neurons to undergo apoptosis You dont have holes in the brain in this case because the clumps dont dissipate Causes progressive memory loss, motor deficits, and eventual death Alzheimers disease Occurs in approximately 10 percent of the population above the age of sixty-five and almost 50 percent of people older than eighty-five years Produces severe degeneration within and around the hippocampus, neocortex (especially the association cortex of the frontal and temporal lobes), and other places Degeneration produces progressive loss of memory and other mental functions Brain of Alzheimers patient versus normal brain Alzheimers disease (AD) is characterised by progressive memory loss and other mental functions. -amyloid (A) Protein found in excessive amounts in brains of patients with Alzheimer's disease When it clumps together because it is misfolded, it forms amyloid plaques Amyloid plaque Extracellular deposit containing a dense core of -amyloid protein surrounded by degenerating axons and dendrites and activated microglia and reactive astrocytes Start to be surrounded by other neural tissues (axons, dendrites, etc.) Tau protein Protein that is a component of microtubules, part of the cell's transport mechanism. Tau protein becomes hyper-phosphorylated in Alzheimer's disease, which disrupts transport. In Alzheimers, the Tau proteins have tons of phosphate groups put on them They break down over time and reforms neurofibrillary tangles Neurofibrillary tangle Dying neuron containing intracellular accumulations of twisted Tau protein filaments that formerly served as cell's internal skeleton This begins to clump up as well -amyloid precursor protein (APP) Protein that is the precursor for -amyloid protein. The gene for this protein is located on chromosome 21, which is the one duplicated (triplicated) in down syndrome. Secretase
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