Cycle 9: Genetics of Diseases Flashcards
How do neurons communicate?
Neurons communicate at the synaptic cleft, where the axon terminal of one neuron meets the dendrite of another. Neurotransmitters like acetylcholine are released into the synaptic cleft to transmit signals.
What happens to cholinergic neurons in Alzheimer’s Disease (AD)?
loss of acetylcholine production and degeneration, leading to impaired memory and learning.
How are beta-amyloid plaques formed?
Beta-amyloid plaques are formed from the cleavage of (APP) by β-secretase and γ-secretase, producing (Aβ) peptides, particularly Aβ42, which aggregates to form insoluble plaques.
What causes neurofibrillary tangles in AD?
Neurofibrillary tangles are formed due to the hyperphosphorylation of TAU proteins, which disrupts neuronal function and leads to cell death.
What are acetylcholinesterase inhibitors?
Acetylcholinesterase inhibitors, like donepezil, inhibit the enzyme that breaks down acetylcholine, increasing its availability in the synaptic cleft.
What is the role of NMDA antagonists in AD treatment?
NMDA antagonists, such as memantine, block excessive glutamate activity, which can be toxic to neurons.
What genetic risk factor is associated with Down Syndrome and AD?
Increased expression of APP due to an extra chromosome 21 leads to early-onset AD.
What mutations are linked to increased Aβ42 production?
Mutations in Presenilin 1 and 2 lead to increased production of Aβ42, which aggregates more readily.
What is the significance of the Apo E4 variant in AD?
The Apo E4 allele is less effective at clearing Aβ aggregates, increasing the risk of AD.
What is inter-tumoral heterogeneity?
differences between tumors in different patients, with each tumor having unique genetic mutations and characteristics.
What is intra-tumoral heterogeneity?
differences within a single tumor, where different regions may have distinct genetic mutations and cellular behaviors.
What is clonal evolution in cancer?
Clonal evolution is the process by which different clones of cancer cells acquire new mutations over time, some gaining a survival advantage and driving tumor progression.
How do cancer cells develop drug resistance?
Cancer cells can become resistant to drug treatment through acquired mutations or epigenetic changes, leading to relapse.
What are driver mutations?
Driver mutations confer a growth advantage to cancer cells and are directly involved in cancer progression.
What are passenger mutations?
Passenger mutations do not contribute to cancer development and are biologically inert, occurring randomly during cell division.
What causes endogenous DNA damage?
Endogenous DNA damage occurs naturally during cell division and metabolism, leading to mutations over time.
What are proto-oncogenes?
Proto-oncogenes promote cell growth and division; mutations can lead to gain-of-function and uncontrolled cell proliferation.
What are tumor suppressor genes?
Tumor suppressor genes regulate the cell cycle and DNA repair; loss-of-function mutations can lead to unchecked cell growth and cancer progression.
What are cancer stem cells (CSCs)?
Cancer stem cells are a small subset of cells within a tumor that can self-renew and differentiate into various cancer cell types, driving tumor initiation and therapy resistance.
What experiment demonstrated the tumorigenic potential of cancer stem cells?
In experiments, CD44+/CD24- cells were isolated and injected into mice; only 200 of these cells formed a tumor, whereas 20,000 non-stem cancer cells failed to do so.
