Lecture 21 - Neurodegenerative Diseases Flashcards
What are neurodegenerative diseases?
Neurodegenerative diseases, like Alzheimer’s, Parkinson’s, Huntington’s, FTD-ALS, and prion diseases, involve the degeneration of neurons, leading to progressive loss of brain function.
What causes neuronal degeneration in neurodegenerative diseases?
Neuronal degeneration is driven by cellular apoptosis, triggered by the accumulation of misfolded proteins that disrupt normal cellular function.
Why do proteins have a risk of clumping together in neurodegenerative diseases?
Proteins can clump together in neurodegenerative diseases because, at high concentrations, their structure can change (misfold). When proteins misfold, they lose their proper shape and are more likely to stick together, forming clumps. These clumps can be harmful to cells and are linked to diseases like Alzheimer’s or Parkinson’s. Misfolding and aggregation prevent the proteins from doing their jobs properly, leading to cell damage.
How does the body prevent proteins from clumping together?
Cells have mechanisms to ensure proteins fold correctly into their 3D shapes and systems for destroying misfolded proteins. However, they struggle with removing aggregated proteins.
What is Parkinson’s disease, and what causes it?
Parkinson’s disease is a degenerative movement disorder caused by the degeneration of dopamine neurons in the substantia nigra, leading to motor problems like rigidity and shaking.
What is the role of alpha-synuclein in Parkinson’s disease?
Alpha-synuclein is a protein expressed in dopamine neurons. Misfolded alpha-synuclein forms aggregates called Lewy bodies, which are associated with neuron degeneration in Parkinson’s disease.
What are Lewy bodies?
Lewy bodies are aggregates of misfolded alpha-synuclein protein found in the cytoplasm of midbrain dopamine neurons in people with Parkinson’s disease.
What role does ubiquitin play in protein regulation?
Ubiquitin tags misfolded or faulty proteins for degradation by proteasomes, which break them down into amino acids for recycling.
What happens when parkin function is lost in Parkinson’s disease?
Loss of parkin function leads to the accumulation of misfolded proteins, like alpha-synuclein, which eventually causes cell death, particularly in dopaminergic neurons.
What is the difference between toxic gain of function and loss of function mutations?
Toxic gain of function mutations produce proteins with harmful effects (e.g., alpha-synuclein mutations in Parkinson’s). Loss of function mutations lead to a lack of essential proteins (e.g., parkin mutations).
What is the treatment for Parkinson’s disease?
Treatments for Parkinson’s disease focus on increasing dopamine signaling, which helps improve motor function. Medications like L-dopa are converted into dopamine in the brain, while dopamine receptor agonists directly activate dopamine receptors to mimic dopamine’s effects. Surgical treatments, such as deep brain stimulation (DBS) and brain lesions, help reduce symptoms by regulating brain activity. These treatments alleviate motor symptoms but don’t cure the disease.
What are the motor symptoms of Parkinson’s disease?
Symptoms include muscle rigidity, slow movement, shaking, difficulty walking, and eventual dementia.
What is dementia?
Dementia is a progressive impairment in memory, thinking, and behavior, often due to neurodegenerative diseases, multiple strokes, or brain trauma.
What is Alzheimer’s disease?
Alzheimer’s disease is a neurodegenerative disorder causing memory loss, motor deficits, and eventual death, typically affecting those over 65 years old.
What is β-amyloid, and how is it related to Alzheimer’s disease?
β-amyloid is a misfolded protein that aggregates in Alzheimer’s disease, forming amyloid plaques in the brain, especially around the hippocampus and neocortex.
What are amyloid plaques?
Amyloid plaques are extracellular aggregates of β-amyloid protein surrounded by glial cells and degenerating neurons in Alzheimer’s disease.
What is tau protein, and how is it involved in Alzheimer’s disease?
Tau is a microtubule protein that becomes hyper-phosphorylated in Alzheimer’s disease, leading to intracellular accumulation called neurofibrillary tangles, which disrupt cell function.
What are neurofibrillary tangles?
Neurofibrillary tangles are intracellular accumulations of twisted tau protein in dying neurons, characteristic of Alzheimer’s disease.
What is β-amyloid precursor protein (APP)?
APP is a protein that is the precursor for β-amyloid protein, and its gene is located on chromosome 21, which is triplicated in Down syndrome.
What is the function of secretase?
Secretase is a class of enzymes that cut the β-amyloid precursor protein (APP) into smaller fragments, including β-amyloid.
