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what is Alzheimer's Diseaseis neurodegenerative (loss or deterioration of neurons) disease and is progressive (can't go back)
explain the structure of neurons and how they communicate at the synaptic cleft"<img src=""paste-608a966cbcc4393f4181276bccbcbe6f89cfd1f8.jpg""><br>at the synapse, neurons communicate via the release of neurotransmitters"
how do cholinergic neurons work-Acetyl Coa from the mitochondria gets converted to acetate<br>- acetate combines with choline, through a reaction which CAT (choline acetyl transferase) catalyzes to make Acetylcholine&nbsp;<br>- aceytlcholine gets released from the cell to the synapse when you have to recall something<br>- when it's does signalling the other neuron, Acetylcholinesterase breaks it back down to acetyl and choline to be uptaken by the pre-synaptic neuron<br><br>
why are cholinergic neurons downregulated in ADCAT expression is very low, thus, can't make a lot of acetylcholine
how can the downregulation of cholinergic neurons be treated"target Acetylcholinesterase (AChE) by inhibiting it; acetylcholinesterase inhbitors; keep acetylcholine the synaptic region for longer<br><img src=""paste-4cd0b1f669a0b46975a5be8364c4cf7b0b2dc0ce.jpg"">"
how are does APP work normally"- a protein called Amyloid Precursor Protein (APP) on cell membrane<br>- alpha-secretase and gamma-secretase cuts peptides and protein is broken down into 2 soluble peptides and recycled through producstion and clearance<br>- another way is Beta-secretase cutting a different part of the protein, creates an insoluble peptide (Amyloid Beta) that has to be cleared by Microglia, Astrocytes and Apolipoprotein E.<br><img src=""paste-4aadae445432eec8298b9d2f72d17c175fc32df6.jpg"">"
how do beta-amyloid plaques formoverexpression of beta-secretase; too many insoluble peptides (beta amyloid) but can't keep up with clearance<br><br>so you have an overproduction of beta amyloid; they become sticky and clump together which become difficult to clear
how does a mutation in gamma-secretase lead to familial alzheimer's"<img src=""paste-86639d62592d6c459054115139cec1c57a3e545e.jpg""><br>the orange protein is an enzyme call presenilin-1 which catalyzes the cutting of the APP; mutations in presenilin lead to familial AD because it causes it to cut at the 42 amino acid which leads to the sticky beta amyloid plaques"
how do plaques kill/damage neurons"- cells see plaque as something foreign; immune cells are activated; this results in inflammation and damage to neurons<br>- this resultes in too much glutamate, which hyperstimulates its neuron through a receptor called NMDA<br>- plaques can also lead to direct neuron death by blocking the synapse<br><img src=""paste-48ee22007b78bc4c1e0fbbf5fbc9cf71a56054bd.jpg"">"
how can the binding of glutamate to its receptor be targeted by treatmentuse an NMDA antagonist which doesn't allow glutamate to bind and form a signal
what do tau proteins domicrotubles work as conveyor belts, brining nutrients/neurotransmitters down the axon<br><br>tau proteins keep the microtubles together (think of them like a nail or screw)<br><br>tau proteins need to by hypophosphorylated
how nuorfibrillary tangles form- tau proteins are hyperphosphorylated and microtubules fall apart<br>- tau proteins clumps and produce tangles
what are the genetic factors of ADdown syndrome: <br>- APP gene coded on chromosome 21; people with down syndrome have increased APP expression and increased risk of early onset Alzheimer's<br><br>mutations in presenilin 1 and 2:<br>- presenilin 1 coded on chromosome 14 and presenilin 2 on chromosome 1<br>- mutant gamma-secretase produces big bet amyloid peptides, (cuts at 42aa) leading to more plaques<br><br>inhertiance of Apo E4 (variant of Apolipoprotein E):<br>- Apo E3 is good at removing beta amyloid plaques<br>- Apo E4 is not good at removing beta amyloid plaques
what is genetic heterogeneity of cancersdifferences in their genomic sequences; differences in their tumours
inter-tumoral vs intra-tumoral heterogeneityinter-tumoral is differences between individuals<br><br>intra-tumoral between cells through single cell genome sequencing
what is precision medicinetreatment and prevention that takes into account individual variability in genes, environment and lifestyle
explain the process of clonal evolution of cancer"tumours evolve through a series of clonal expansions; one cell gets mutated, then there are more cells that have that mutation; a second mutation is introduced and then a third and so on and so forth<br><br>some mutations need other mutations to drive clonal expansion<br><img src=""paste-df43e5ad62caff6bc5d191b566876551ae327036.jpg"">"
what does chemotherapy targetrapidly proliferating cells (rapidly dividing)
how do cancer cells become resitant to drug treatmentbecause of genetic heterogeneity; one personalized treatment for a specific clone may not work for another clone
driver vs passenger mutationsdriver mutation:<br>- causality implicated in oncogenesis<br>- conferred growth advantage on the cancer cell<br>- positively selected in the microenvironment of the tissue in which the cancer arises<br>- often required for the maintenance of the final cancer<br><br>passenger mutation:&nbsp;<br>- not selected<br>- not conferred growth advantage&nbsp;<br>- not contributed to cancer development
proto-oncogene vs tumour-supressor geneproto-oncogene:<br>- if mutated, will lead to cancer<br>- growth factor receptors -- gain of function mutations -- eg RTK<br><br>tumour-suppressor gene:<br>- protect us from getting tumours<br>- when mutated, can cause tumours<br>- cell cycle checkpoint and DNA repair -- loss of function mutations -- eg. p53<br>
explain cancer stem cells- many stem cells in the niche can be cancerous<br>- cancer stem cells are slow dividing cells -- therefore chemotherapy won't work
explain the experiment in mice that proved stem cells drive oncogenesis"injected tumour cells in mice and then injected cancer stem cells in other mice; the mice injected with the cancer stem cells formed a tumour<br><img src=""paste-b4f8314a32b24849a617399a96762fadc4d8a073.jpg"">"
what do cancer cells have to overcome in order to be sucessfulproliferation -- rapid division<br>anti-apoptosis -- no programmed cell death<br>growth<br>motility'<br>invasiveness<br>angiogenesis -- growth of new blood vessels<br>escape immune surveillance