Speculative questions of Bio 4510 Midterm II
??? 1--Current data suggest accumulation of amyloid plaques and Tau lead to Alzheimer’s disease. The disease leads to the progressive loss of memory. Provide a speculative series of events (use signaling pathways if applicable) that would lead to the progressive degeneration of memory function. Is there a way to measure the changes?
Oct 15
AB amyloid signaling protein which induce toxicity
AB dimer will lead to hyperphosphorylated Tau causing tangles, protesome, Ca dysfunction, and mitcohondria will create ROS.
Tau stabilizes MT but overexpression of Tau has detrimental effect
Since mGluR2 contribute to memory disorder, A speculative series of events that can lead to progressive degeneration of memory function Is activation or mGluR5 receptor is consistently turned on.
When a glutamate neurotransmitter bind to a mGluR5 receptor, it leads to a series of events. These series of events causes G protein Q to activate (talk about Heterotrimeric protein slide?) which cause Phospholipase C to cleave and result in second messenger DAG to activate PKC (by DAG Ca and PS bind to regulatory unit of PKC , enzymatically activating catalytic unitm and phosphorylating CREB?) or IP3 to activate Ca release from the ER (Ca/Calmodulin kinase (inactivated folded) activated by Ca/Calmodulin binding to regulatory unit then enzymatically activating catalytic unit to phosphorylate). A way to measure these changes would be to …..
Follow flur protein to show expression , stain, of ab and mglur over time. More expression causes more degeneration going on bc they are bad for memory. If more being expressed then its worse. look at dendrite are where tau and ab protein and if something is toxic they look different. see if memory of subj is getting worse if u see changes at kinase level and expression level.
Measure is mglur active over time and if so how do the dendrites look?
Test over time.
Since mGluR5 receptor binds to AB amyloid protein, series of events that would lead to progressive degeneration of memory function. mGluR5 is metabotropic and will induce signaling pathway
AB bind to mGluR5 -> G protein activated -> Phospholipase C etc [pg 23 Oct 24 lecture]
****2--Myasthenia Gravis is an autoimmune disease leading to the loss of Acetylcholine receptors. A current treatment uses an acetylcholinesterase inhibitor to temporarily rescue muscle response. Based on your knowledge of the Acetylcholine receptor/signaling, speculate on a different strategy to ameliorate the symptoms (not blocking AchR antibody production)?
Ach are located in the NMJ and CNS synapse. They act on Ionotropic nicotinic receptors. Agonist and Antagonist bind to the AchR at the post synaptic terminal to create a synapse/response. In Myasthenia Gravis, an autoimmune disease leading to muscle weakness and fatigue. Different strategies to ameliorate the symptoms can be to
Agonist for Ach receptor, Increase level of receptor activation, which increase the number of Ach and increase synthesis of Ach. To accommodate what has been lost for Ab. Temp rescue muscle response
Make more Ach
a. Quantal packets of Ach neurotransmitter (Ach is package of discreet vesicles (quantal packets) which allows measure released via exocytosis).
b. The Vesicular transporters are highly selective and only are released in quantal packets. In MG, the MEPP amplitude is less than a person without MG. So by stimulating the NMJ and create a AP you Can create enough MEPP to create a full blown EPP (end plate potential) to stimulate the axon/ the muscles and have a lot of Ach floating around.
>> Without stimulation of a muscle a person can become paralyzed.
1. Since you’re losing AchR you can increase/stimulate/over create amount of Ach being made. Because you want to create a stimulus/keep making more Ach to prevent the loss of Ach receptors and regenerate AchR
2. ?? Inhibit breakdown of Ach would get Ach would be
