L12 Flashcards
(33 cards)
What is Parkinson’s disease (PD)?
A chronic, progressive neurodegenerative movement disorder characterised by tremor, stiffness, bradykinesia, and non-motor symptoms like anosmia, depression, and sleep disturbance.
What causes Parkinson’s disease?
Progressive loss of dopaminergic neurons in the substantia nigra; often idiopathic. Neuromelanin accumulation indicates neuronal loss.
What are the primary motor symptoms of PD?
Resting tremor, muscle rigidity, and bradykinesia (slowness of movement).
What is the therapeutic aim in PD?
To increase dopamine transmission in the striatum to improve motor function.
Which drugs reduce dopamine signalling and worsen PD?
Antipsychotics and antiemetics can reduce dopamine signalling and cause drug-induced Parkinsonism.
What are the dopamine precursors?
Tyrosine and L-DOPA.
What else does dopamine produce?
Noradrenaline (NA).
What are the broader system-level effects of dopamine loss in PD?
↓ NA, altered reuptake, compensatory hyperactivity, cognitive deficits, worsened motor symptoms, and mood disturbances.
How is the basal ganglia affected in PD?
Loss of dopamine causes overactive ACh in the striatum → thalamic inhibition → bradykinesia.
What are the symptomatic treatments for PD?
Levodopa, dopamine agonists, MAO-B inhibitors (e.g. selegiline), COMT inhibitors (e.g. entacapone).
What is cross-talk in PD?
Interaction of multiple neurotransmitter receptors at the same synapse affecting dopamine signalling.
What is amantadine used for in PD?
An NMDA antagonist that increases dopamine release and blocks reuptake.
Why is carbidopa given with levodopa?
Carbidopa inhibits peripheral conversion of levodopa to dopamine, increasing CNS availability and reducing side effects.
What is the downside of levodopa + carbidopa therapy?
Can cause peripheral toxicity and less metabolism in the GI tract.
What are side effects of levodopa?
Non-motor: nausea, orthostasis, hallucinations; Motor: dyskinesias.
What are side effects of dopamine agonists?
Nausea, sleep attacks, hypotension, compulsive behaviours, oedema.
What are disease-modifying therapies under development for PD?
α-synuclein targeting, LRRK2 inhibitors, antioxidant therapies, GBA modulators, gene therapy, anti-inflammatory strategies.
What is Alzheimer’s disease (AD)?
A chronic neurodegenerative disease causing progressive loss of cognitive function, beginning in the outer cortex.
What causes dementia?
Alzheimer’s is the most common cause of dementia.
What are the two pathological hallmarks of AD?
Extracellular amyloid-β plaques and intracellular tau neurofibrillary tangles.
What is the amyloid cascade hypothesis?
Mutations in APP, PSEN1/2, or trisomy 21 lead to excess toxic Aβ42 → aggregation → neuronal death → dementia.
How is APP processed in AD?
Amyloidogenic: APP → β-secretase → Aβ (toxic); Non-amyloidogenic: APP → α-secretase → non-toxic p3.
What is γ-secretase?
A complex (PSEN1, PEN2, APH-1, nicastrin) that cleaves APP, influencing Aβ42 production.
What are the APP-related mutations?
Some increase toxic Aβ42 (e.g. London), others are protective (e.g. Icelandic).
