Exam 3 Flashcards

Question

What is the P wave in an electrocardiogram?

Answer 1

record of atrial depolarization

Answer 2

record of movement of ventricular depolarization

Answer 3

corresponds to the time when the ventricle is contracting but no electricity is flowing through it. The ST segment usually appears as a straight, level line between the QRS complex and the T wave.

Answer 4

corresponds to the period when the lower heart chambers are repolarizing.

Answer 5

``` Ejection fraction o Diastolic dysfunction: Mitral Inflow: E (filling of the ventricle) /A(filling of atrial expect only a little filling of the mitral valve but if large inflow back have a lot back in atrium) ➢ Blood flow across the mitral valve is assessed with dopplar, 2 waves are seen: ➢ E wave (filling of ventricle) ➢ A wave (filling of atrial) Thickened ventricle Cavity size o Wall motion abnormailty o Valve assessment o Hypertrophic cardiomyopathy LVMI: Left ventricular mass index ```

Answer 6

o Speckle-tracking strain image analysis Myocardial deformation Regional variation in wall synchronicity indicative of ventricular function *uses speckle tracking algorithm to monitor the deformation of the endocardium *Measures the shortening of the cardiomyocyte (strain) and the rate at which this deformation occurs (strain rate) *shown to be more sensitive to regional variation in ventricular function

Answer 7

o Heart has high energy demand, therefore, rich in mitochondria => susceptible to oxidative damage o Overexpressing catalase in the mitochondria with a decreased LMVI. o E/A ratio diastolic disfunction protecting free radical production protects form age-related declines o Polg mice: homozygous mutation in mitochondrial polymerase (proofreading for mutations) gama causing increases in mitrochondrial DNA mutations o MCAT shows better with the mutated mouse. Protecting from reactive oxygen specie sin the mitochondria specifically leads to increased life span. Looking at left ventricular mass, hypertrophy with age and wild type see increase in left ventricle size. overexpress catalase protecting from increase so not increasing as much as the wild type. As a measure of diastolic disfunction measuring E/A ratio where they see wild type with age increase in diastolic dysfunction. increasing catalase in the mitochondira leads to less diastolic disfunction although it does increase with age.

Answer 8

Homozygous mutation of mitochondrial polymersaase gamma mutation leading to decreased proofreading capabilities leads to substantial increases in mt DNA mutations and deletions. Polyg m/m mice display an accelerated cardiac aging phenotype that is rescued by overexpressing mCAT. With age greater increased in ventricular mass and don't see a statistically significant increase in the wild type mouse. increased cardiac aging types with. Don't see increased in left ventricular mass in wild type, mCAT significantly decreases on the double mutant suggesting ROS playing role in aging heart. E/a Ratio shifting to the lower ratio indicating diastolic dysfunction with age. Polgm/m myocytes display increased cellular senescence and apoptosis that is rescued by overexpressing mCAT.

Answer 9

o Rapamycin Protects Against Cardiac Hypertrophy Induced by Angiotensin II. Angiotensin II: Hormone that causes vasoconstriction and increase in blood pressure that ultimately leads to heart failure. Aldosterone can also lead to fibrosis less contractability and less heart function. o Rapamycin Protects Against Angiotensin II-Induced Increase in Protein Synthesis. Rapamycin inhibits the activation of S6 that leads to increase protein synthesis associated with cardiac hypertrophy! Increased phosphorylation of S6, treating with rapamycin with increasing doses large increase in phsophoryaltion of S6 and rapamycin suppresses the increases. reduction in S6 phosphorylation reducing cardiac hypertrophy seen in this model o Rapamycin suppresses pressure overload-induced increase in myocyte size. Did surgery to restrict aorta. Show an increase in ventricular size and an increase in myocyte size showing hypertrophy. With rapamycin inhibiting tor in control no difference, and reduce size of myocytes for those that had surgery. o Rapamycin: reduced cardiac inflammation and improved cardiovascular functions (LV function and cardiac hypertrophy). Looking specifically at the E/A ratio. Better contraction and a better release. o Young mouse have rapamycin and calorie restriction improving cardiac function in old muce. Improved E/A ratio with calorie restriction. Attribute to better mitochondrial function and biogenesis.

Answer 10

Protects against cardiac hypertrophy and age-related decline in LV Function Mechanistically: Inhibits protein synthesis, potentially reducing the increased size of myocytes seen with age Enhances RAD expression (unclear if direct target of mTOR). calcium signaling inhibiting hypertrophy. Similar cardiac improvement as Calorie Restriction

Answer 11

angiotensin-aldosterone system adrenal signaling insulin signaling o

Answer 12

In mice, decreased insulin signaling attenuates age-associated cardiomyocyte dysfunction. In isolated cardiomyocytes ability to contract on a dish in response to insulin. In contrast, in humans, there is a decline in serum IGF-1 with age that correlates with an increased risk of heart failure! Increasing IGF-1 in humans may be beneficial under conditions of heart failure.

Answer 13

``` Pericardial fat accumulation Coronary blood vessel rigidity Collagen/elastin increase Decreased contractile deficiency Lipofuscin accumulation Heart valve thickening Pacemaker cell number decline Vein dilation and stretching Coronary artery integrity weakens ```

Answer 14

``` Longer beat recovery required Increased incidence of arrythmia Skipped/extra beats Cardiac output (blood vol/min) decline Increased incidence of fibrillation and electrical impulse block Increased blood vessel rigidity Slight plasma volume decreases ```

Answer 15

``` Inflammatory Response Formation of Foam Cells Foam Cells Weaken Arterial Wall Over time, plaque calcifies Can be released and cause blockage (embolus) ```

Answer 16

Estimates blood flow velocity using frequency changes

Answer 17

``` E/A Blood flow across the mitral valve is assessed with dopplar, 2 waves are seen: E wave (filling of ventricle) A wave (filling of atrial) Thickened ventricle Cavity size Wall motion abnormailty Valve assessment Hypertrophic cardiomyopathy LVMI: Left ventricular mass index ```

Answer 18

``` Changes in Body Composition ( increases in fat as you age with a decline in physical activity and a decline in food consumptiona) nd Energy Metabolism (muscles utilize half resting energy expenditure with reducing mass reducing metabolism) Decreased Muscle Mass: Sarcopenia Changes in the Skin Changes in the Senses: such as Hearing: presbycusis and Vision: presbypia, cataracts Changes in the Digestive System Changes in the Immune System Changes in the Reproductive System ```

Answer 19

loss of muscle cell number and cell size

Answer 20

slow touch endurance type activites such as running a marathon and maintain posture antigravity muscle

Answer 21

fast twitch with short-term intense or powerful movements such as hitting a baseball and they decrease the most with age.

Answer 22

Loss of subcutaneous fat, Thinning dermis, and Loss of collagen fibers (providing structure to dermis

Answer 23

o Primary cause of the age-related decline in hearing is alterations to the inner ear: Loss of hair cells, Loss of stereocilia in the organ of Corti (Reduced release of neurotransmitters resulting in decreased ability to detect l and loudness and higher pitches).

Answer 24

inability to focus on close objects and it Affects ALL individuals over the age of 50, Due to inability to replace or repair damaged cells in the lens and collagen becomes stiffer with age

Answer 25

opacity in the lens of the eye: At the interface between normal aging and disease, and May be due to reduced Unfolded Protein Response with age!

Answer 26

Innate Immunity: neutrophils and/or macrophages phagocytose foreign particles. Phagocytic function declines with age; numbers do not decline

Answer 27

Adaptive Immunity: dendritic cells activate; lymphocytes -- T cells(helper cells activating B cells to clear pathogen or cytoxic cells secreting things that kill invader via its apoptosis) and B cells – protect against invaders that bypass the innate immune system Production of naïve T cells, number of B cells, and effectiveness of antibodies ALL decline with age!

Answer 28

Non-connected organs and glands, each of which secretes hormones directly into the blood, and have affects on global homeostasis Regulates: metabolism, growth and development, maintenance of blood glucose Age-related decline in ALL endocrine organs and glands Pineal gland: Regulates body’s biological rhythm Thyroid: Increases metabolic rate Pancreas: Affects glucose homeostasis

Answer 29

Glucose enters pancreatic β-cell through GLUT2 Glucose is metabolized Rise in ATP closes the ATP-sensitive K+ channels and prevents K+ ions from leaving the cell This causes the inside of the cell become more positive (depolarized) Voltage-dependent Ca2+ channels to open Ca2+ will diffuse down concentration gradient into the cell Ca2+ causes insulin-containing vesicles to fuse with membrane and insulin to be secreted by exocytosis.

Answer 30

normal method which triggers DNA replication machinery P53 is the gatekeeper of the genome and it is activated in stressful situations where proteins then phosphorylate p53 which accumulates in the cell. then p53 (transcription factor) binds to p21 promoter and p21 halts the cell cycle at this point.

Answer 31

Dna damage telomere shortening stress

Answer 32

ER chaperones in the unfolded protein response. ER stress occurs when too many damaged or “unfolded” proteins are present activating the Unfolded [rotein response with the purpose is to refold damaged proteins. If you cant do that then you apoptose the cell.

Answer 33

egradation of intracellular components in lysosomes, including damaged organelles and damaged biomolecules, components are then recycled for use in making new proteins, lipid and to synthesize new DNA

Answer 34

• two main functionso of autophagy, such as an alternative source of energy (during starvations. Cellular quality control (degrade damaged proteins) to turnover of cellular components and removal of damage before they interfere with normal cell function.

Answer 35

Modulators of autophagy with nutrient signaling (starvation activates autophagy) such as mTOR, Ras/PKA, Insulin activating autophagy due to starvation. Stress response (damaged biomoleculesactivate autophagy such as ER stress, hypoxia, oxidative stress, pathogen infection.

Answer 36

mTor (mechanistic target of Rapamycin)- when nutrients are high, mTOR is activated to promote protein synthesis and inhibit autophagy through the phosphorylation of ULK1 but when mTOR is inhibited, the “brakes” are relased and autophagy will ensue. Inhibitors of this pathway are rapamycin and analogs, Torin1 PP242. When mTOr is activte inhibiting ULK complex.

Answer 37

inhibits it by phosphorylation not allowing it to enter the nucleus inhibits it

Answer 38

mTor (mechanistic target of Rapamycin)- when nutrients are high, mTOR is activated to promote protein synthesis and inhibit autophagy through the phosphorylation of ULK1 but when mTOR is inhibited, the “brakes” are relased and autophagy will ensue. Inhibitors of this pathway are rapamycin and analogs, Torin1 PP242. When mTOr is activte inhibiting ULK complex. when reduced in all organisms they have extended life span

Answer 39

insulan binds causing autophosphoryaltion of its receptor and the other things bind akt is then activated by phosphorylation by PDK1 and this is inhibited by Fox01.

Answer 40

glucose uptake and storage, cell proliferation and growth, cell survival and promotes protein synthesis by activating indirectly

Answer 41

Akt inhibits fox01 which inactivates the transcription of p21 allowing activation of cyclin D and E making the cell cycle go through G1 and into the S phase o akt phosphorylates and inhibits p21 c allowing activation of cyclin D and E making the cell cycle go through G1 and into the s phase

Answer 42

Daf-2 insulin receptor • age-1- Phosphoinositide 3-kinase phosphorylating pip2 to pip3 is inhibited by daf-16 • daf-16- fox01 need daf16 working for autophagy to extend daf2 lifespan • akt is the same

Answer 43

binds mTor, PRAS and raptor and leads to protein translation (S6K and 4E-BP1), lipid biogenesis (SREBPs), and inhibited autophagy (ULK1)

Answer 44

binds main, rector and mTor cytoskeletal changes (PKCalpha), cell survival (akt) and stress response (SGK1)

Answer 45

akt in high nutrients, and ERk in high nutrients they function to inhibit the tsc complex

Answer 46

leads to gluconeogenesis, cell death, detoxifies, repairs DNA and arrests G1 and G2

Answer 47

lifespan, affecting cancer, cardiovascular disease, neurodegeneration, immune system, and aging. It has negative side affects including aphthous ulcers, edema, hyperlipidemia, immune suppression, glucose intolerance, and reduced male fertility.

Answer 48

it deacetylates it meaning that p53 cannot unwind and transcribe p21 meaning the cell cycle is not stopped as it should be when p53 senses DNA damage

Answer 49

uptakes glucose by muscles and adipose tissue through Glut 4 translocation (activated by exercise) glucose storage inhibiting gluconeogenesis in the liver and activating glycogen formation

Answer 50

Diabetes mellitus: Caused by the inability of cells to take up glucose from the blood. insulin is still produced but cells develop a resistance to the action of insulin. developing after the age of 40 affecting 20-25% of the population type I diabetes with insulin resistance eventually leading to impaired beta-cell function but need both to have this type of diabetes with risk factors such as obesity, age, excess food, genes, sedentariness, and stress

Answer 51

``` Caused by insufficient insulin secretion Autoimmune disease resulting in attack and eventual death of pancreatic beta-cells Genetic and viral causes Concordance rate in identical twins is 30% ```

Answer 52

The inability of insulin to effectively induce glucose uptake by various tissues, when secretion remains normal with an unknown mechanism as the number and affinity of insulin receptors not changing nor GLUT 4 levels but the translocation is reduced

Answer 53

Increased p16 expression with Age Activation of UPR-induced beta-cell apoptosis Activated FoxO1 causes beta-cell dedifferentiation by translating BIM as well as regressing back to simpler cells, then dedifferentiating into alpha-cells reducing beta number of beta cells.

Answer 54

p16 expression increases with age Beta-cells have limited proliferative capacity, BUT this declines with age Any damage to beta cells later in life cannot be undone p16: Normally inhibits cyclin D/cdk4 complex Increased p16 expression is associated with age-related decline in islet proliferation with hyperglycemia inducing the unfolded protein response in bet-cells leading to beta-cell apoptosis Activation of IRE1, PERK, and ATF6 transmembrane receptors activates gene transcription for chaperones (to help refold proteins) or apoptosis if damage is too great!

Answer 55

Increased translation of insulin mRNA activates UPR by binding to chaperones in order to process insulin!

Answer 56

impaired microvascular blood flow due to increased glycoslation of collagen(part of ECM) happening to tendons, ligaments, skin, bone, blood vessels, cartilage, dentin, and heart valves leading to a loss of flexibility

Answer 57

cardiomyopathy- deterioration of the myocardium (heart muscle) leading to heart failure neuropathy- damage caused to peripheral nerves patient can't sense tissue damage retinopathy-restriction of retinal blood vessels leading to vision loss or blinds

Answer 58

with rapamycin aded there was reduced cardiac inflammation, and improved cardiovascular functions such as LV and less cardiac hypertrophy

Answer 59

Renin-Angiotensin-Aldosterone System ACE inhibitors or receptor blockers reduces age-dependent cardiac pathology o

Answer 60

B-Adrenergic Signaling Chronic β-Adrenergic Signaling is deleterious to heart, receptor for epinephrine or adrenaline resulting in the fight or flight response increasing the metabolic demand on the body because of increased heart rate, contratibility, afterload (blood pressure), and wall stress. Increase metabolic demand due to increased heart rate, contractibility, afterload (blood pressure), and wall stress In human trials, beta-blockers (block receptor) protect against heart failure

Answer 61

sensory input to CNS

Answer 62

CNS to motor output

Answer 63

integrate sensory input to motor output

Answer 64

Schwann cells | oligodendrocytes

Answer 65

o Voltage-gated ion channels: o Movement of Na+ and K+ into and out of the cell o Initiating Event o Membrane becomes more permeable to Na (-55mV) o Causes Na channels to open (+30mV) o K channels open and initiate repolarization

Answer 66

Used at neuromuscular junction (ie activates muscles) 1. Nicotinic Receptor: propagates signal by opening Na channels on postsynaptic neurons • Important for attention, learning, memory • Degradation of neurons with nicotinic receptors is involved in the progression of Alzheimer’s disease 2. Muscarinic Receptor: uses a G-coupled receptor mechanism to propagate signal. • Primarily found in heart and lung; decreased in these receptors in the heart leads to functional decline in cardiac function

Answer 67

1. Dopamine: “Pleasure and Reward” 2. Norepinephrine: “Rest and Digest” 3. Epinephrine (Adrenaline): “Fight or Flight” o Can bind to 2 different receptors: Alpha-adrenergic receptors: propagate signaling by modulating ion channels Beta-adrenergic receptors: use the G-coupled receptor signaling pathways to propagate signaling Loss of function of adrenergic neurons is the primary cause of Parkinson’s disease

Answer 68

Perform a specific task at a specific location | Once formed, cannot be replaced; terminally differentiated

Answer 69

Astrocytes: Maintain extracellular environment for neurons by regulating ion levels and recycling neurotransmitters Most abundant Form basis for blood-brain barrier by regulating vasoconstriction and vasodilation Oligodendrycytes: Produce myelin, the protein that coats axons and improves electrical conduction

Answer 70

Mobile macrophages capable of phagocytosis and initiating the inflammatory response

Answer 71

o Physiological Mechanism that Protects Brain from Insult, Main Purpose is to inhibit infectious particles (ie bacteria), from getting into the brain

Answer 72

none are uniform and it depends on the brain and individual loss in cell number in hippocampus and cerebellum glial cell formation increases with age reduced capacity to rid itself of damaged proteins with accumulation of amyloid plague and neurofibrillary tangles not significantly affecting changes

Answer 73

o Aβ protein o Protein forming the plaques o Secondary structure: β sheets o Wrap around each other to form insoluble aggregates o No (known) specific catabolism pathway to remove plaques o formed from APP then the enzyme B secretase predominates in neural tissue leading to the production of the potentially neurotoxic Aβ protein with decreased chaperones with age leading to progression of Alzheimer;s

Answer 74

o Insoluble twisted fibers found inside brain cells o Normally, microtubules perform a vital function by directing the movement and determining the final position of the organelles from the cell body to the axon o Tau protein binds to the microtubules and provides stability o Ability to bind depends on its phosphorylation status o Hyperphosphorylated Tau weakensmicrotubule structure leading to degeneration o PHF: insoluble aggregates

Answer 75

blood brain barrier (permeability increases because of ROS affecting tight junctions) small size changes small changes in number of neurons no changes in neuroglia

Answer 76

memory attention learning decision making

Answer 77

no significant loss of neurons | impaired neuronal function underlies cognitive decline

Answer 78

Cell Excitability (the ability to elicit an action potential) declines with age Hippocampus Increase in magnitude of Afterhyperpolarization (AHP) Hippocampus Decreased synaptic strength Primary Cause of Cognitive Decline!

Answer 79

(loss of synaptic contacts, decreased transmitter release, reduced postsynaptic responsiveness to transmitter)

Answer 80

Ca2+ Hypothesis of Aging Altered Ca2+ homeostasis accounts for age-related changes seen in the brain Oxidative Stress and the Aging Brain Free Radical Theory on Aging Vitamin E Supplementation is neuroprotective in mice and protects against AB toxicity Ceberbrovascular Changes with Age Cerebral blood flow decreases with age

Answer 81

chronic, neurodegenerative disease, that worsens over time and is the most common form of dementia Characterized by plaques and tangles(unclear why) loss of connection and eventual death of neurons and brain shrinkage Degeneration of neurons leading to shrinkage of important areas of the brain: frontal (reasoning), temporal (language), occipital (hallucinations), hippocampus (memory)

Answer 82

``` Early-onset: Rare, diagnosed before age 65 Usually in Down’s syndrome patients Late-onset: Diagnosed after age 65 80-90% of cases No significant family history Familial: Direct genetic component: linked to chromosomes 1, 14, and 21 Affects patients in their early forties ```

Answer 83

Potential Explanations: Plaques form between neurons: Block signaling, Activate inflammation, resulting in neuronal death Tangles found inside neurons: Structure of neuron deteriorates, resulting in neuronal death Genetics Environment

Answer 84

Apolipoprotein E ε4 (ApoE ε4)- Normally produced by the liver to transport cholesterol out of the blood. Half of the individuals who develop late-onset Alzheimer’s have this allele with Mice overexpressing APOE ε4 showed significant damage to the tight junction cells in the BBB

Answer 85

``` Modulate APP Targeting secretase Targeting clearance Targeting aggregation Targeting Tau Protein Inhibiting phosphorylation (GSK-3B) Microtubule stabilization Enhancing Tau degradation Modulating Levels of neurotransmitters (CURRENT TREATMENTS) Targeting Oxidative Stress Anti-inflammatory therapy ```

Answer 86

the inability of cells to stop dividing with many regulators in the cell cycle are mutated in cancers with p53 commonly mutated.

Answer 87

Challenged the current ideas at the time that human life is extendable, but that human morbidity has a fixed age at onset. “The Failures of Success” Medicine would continue to move the age of death upward, but the average onset of morbidity would remain the same, thus… the length of period of ill health toward the end of life would increase

Answer 88

exercise, morbidity postponed 10-16 years and mortality 3-7 years

Answer 89

• Rapamycin ahs protective effects with treatment improving age-related conditions such as cancer (inhibits cell proliferation nd cell cycle), cardiovascular disses (affecting hormones), neurodegernation (rapamcin inhibits the production of proteins to form aggregates) , immune system and aging

Answer 90

anti-diabetic drug that reduces blood glucose levels without inducing hyperglycemia

Answer 91

Increased insulin sensitivity Elevated uptake of glucose in peripheral tissues Predominantly… Suppresses hepatic gluconeogenesis metformin targets OCT1 passively diffusing through cell membranes and accumulating in mitochondrial matrix with a positive charge stating there.

Answer 92

* . Inhibits complex 1 of the electron transport chain with reduced ATP and increase AMP:ATP ratio. AMPkinase affects on lipogenesis and gluconeogenesis decreasing. * Increases in AMPkinase in different cells by looking at its substrates. * AMPkinase phosphorylates CRTC2 regualtor of glucose phosphorylates and degrades it decreasing gluconeogensiss making less glucose in the cell. Glucose lowering products were explicitly due to metformin. 3 Days of retformin of mice that are diabetic and with the knockout mouse there is no longer a reduction with metformin because they knocked out an AMPkianse activator showing AMP kinase is necessary. Reduced metformin levels in either mouse with or without knockout. Higher amounts of glucose they have much more normal clearance than untreated mice with knockout having a similar trend suggest AMPkinase with the knockout does not have an effect.

Answer 93

worms-extended life span drosophila-none humans-with diabetes-extended In patients metformin reduces cancer, cardiovascular disease

Answer 94

grew them, treated them, calculated the protein concentration, separated out the concentration nd found the concentration that best fit with what we wanted, loaded the gel, load gel and run it, remove gel and transfer protein then electro it again, block the sample to ge the sticky parts so no antibodies and add the antibodies, develop it with enhanced chemiluninesce, strip it and quantify with image j

Answer 95

Diabetes Mellitus is caused by the inability of the body to uptake glucose from the blood. It is defined as a resting blood glucose above 125 mg/dl. Essentially, insulin is still produced by the beta cells, but cells develop a resistance to the action of insulin. It is thought that this resistance is due to a decrease in the translation of the glucose receptor, GLUT4, to the surface of the cell. After a period of insulin resistance, beta-cell function then declines. Three causes of beta cell dysfunction are increased expression of the cell cycle inhibitor, p16, leading to inhibited proliferation of the beta-cell, activation of beta-cell apoptosis, and beta-cell dedifferentiation. All of these processes, ultimately result in reduced beta-cell mass, which contributes to the progression of Type II diabetes.

Answer 96

Echocardiogram can measure minute changes in cardiovascular function with age. It can measure many parameters of the heart including the ejection fraction, or the amount of blood that is pumped out of the heart. In addition, it can measure diastolic function. This can be measured by examining the E/A ratio (ie how much blood fills the ventricle during diastole as compared to the atria), fibrosis of the ventricle (measured by thickness of the heart), and overall size of the left ventricle (hypertrophy). You can use further software to measure wall motion abnormalities that occur with age.

Answer 97

Metformin is a drug currently used to treat Type II diabetes. It primarily targets the AMPK pathway and is thought to promote longevity because of this pathway. Many age-related diseases, including cardiovascular disease and cancer, are improved after prolonged treatment with Metformin. Rapamycin is another drug that we have talked about that has a potential to extend human life. Rapamycin targets the mTOR protein. While treatment of model organisms with rapamycin has been shown to extend their lifespan, negative side effects do exist, incluing gluose intolerance and reduced immune system function. Rapamycin has been shown to improve many age- related diseases including cardiovascular disease and cancer.

Answer 98

1. Rapamycin protects against increased protein synthesis in the heart 2. Rapamycin suppresses load-induced increase in myocyte size 3. Rapamycin protects from a range of functional cardiac activities, including diastolic dysfuction

Answer 99

Three main ways to target Alzheimer’s disease are to (1) target the amyloid plagues, (2) target neurofibril tangles, and (3) modulate the actual number of neurotransmitters in the diseased brain. This can be accomplished by affecting the aggregation of amyloid proteins by reducing the enzyme that cleaves the amyloid protein (secretase), targeting the clearance of the aggregates (autophagy), or inhibiting the aggregation of the proteins. Tangles occur when the tau protein becomes hyperphosphorylated resulting in reduced stabilization of the microtubules. The formation of tangles can be inhibited by affecting the kinase that phosphorylates tau (GSK-beta), stabilizing microtubules by a different mechanism, or targeting the degradation of tau. Since the progression of the disease results in the degeneration of neurons, often replacing the neurotransmitters is used to treat the disease.