Parkinsons Flashcards
(55 cards)
What are the core similarities between Alzheimer’s disease and Parkinson’s disease?
Both are neurodegenerative diseases.
Misfolding and aggregation of physiological proteins into pathological forms.
Accumulation of aggregated proteins in affected neurons causes dysfunction.
Both can lead to dementia in some patients.
Both are age-related conditions.
What are the main differences between Alzheimer’s and Parkinson’s disease in terms of pathology and affected brain areas?
Alzheimer’s spreads from one brain region to others; Parkinson’s is classically localized.
Parkinson’s affects regions involved in movement (e.g., substantia nigra).
Alzheimer’s affects regions involved in short-term memory (e.g., hippocampus).
Pathological proteins differ:
Alzheimer’s: tau tangles and amyloid-β plaques
Parkinson’s: alpha-synuclein forms Lewy bodies
What are the primary clinical symptoms of Parkinson’s disease?
Movement disorder: tremor, rigidity, and shuffling gait.
Difficulty initiating movement; once started, difficulty stopping.
Resting tremor that can be severe and distressing.
Motor symptoms emerge typically after 80% of substantia nigra dopaminergic neurons are lost.
Who is most affected by Parkinson’s disease and how common is it?
Primarily affects individuals over age 65.
Juvenile cases exist but are rare.
Second most common neurodegenerative disease after Alzheimer’s.
Affects 3–5% of people over 65.
Alzheimer’s affects 1 in 16 over 60 and 1 in 3 over 90.
What causes the clinical symptoms in Parkinson’s disease?
Loss of dopaminergic neurons in the substantia nigra.
Substantia nigra modulates motor signals via dopamine release.
Loss leads to impaired fine-tuning of voluntary movement.
Result: tremor, rigidity, bradykinesia, and postural instability.
What anatomical structure is primarily affected in Parkinson’s disease?
The substantia nigra in the midbrain.
It contains highly pigmented dopaminergic neurons.
In Parkinson’s disease, these neurons degenerate and lose pigmentation.
Why does Parkinson’s disease often go undiagnosed until late stages?
Neuronal death can occur over decades.
Remaining neurons compensate by taking over function.
Symptoms appear only after ~80% neuronal loss.
Leads to late diagnosis and limited treatment options.
How does the motor system control voluntary movement and how is it affected in Parkinson’s?
Movement is initiated in the motor cortex and modulated by midbrain regions like the basal ganglia and substantia nigra.
Dopamine modulates motor output: stimulates movement via basal ganglia.
Parkinson’s disrupts this modulation, causing unrefined or impaired movement (e.g., tremor, shuffling gait).
What experimental lesion model demonstrated the role of substantia nigra in motor control?
Lesion studies in rodents with electrodes targeting substantia nigra.
Sham: electrode inserted, no current — served as control.
Incomplete lesion: ~60% neuronal loss.
Complete lesion: ~70% loss, severe motor deficits.
Tyrosine hydroxylase staining confirmed neuronal loss.
What behavioural tests confirmed motor deficits in the substantia nigra lesion model?
Open field test: measured total distance travelled — less movement with more lesion.
Rotarod test: mice placed on rotating rod — those with lesions fell off faster due to motor weakness.
These tests showed direct link between substantia nigra loss and locomotor impairment.
How did MPTP exposure reveal environmental causes of Parkinson’s disease?
In the 1970s–80s, young drug users in New York developed Parkinsonian symptoms.
They had accidentally synthesized MPTP, a neurotoxic contaminant.
MPTP caused selective death of dopaminergic neurons in the substantia nigra.
Led to early-onset, irreversible Parkinson’s symptoms.
What experiment confirmed MPTP causes dopaminergic neuron death?
Monkeys were injected with MPTP.
Substantia nigra showed massive neuron loss post-exposure.
Behavioural changes: decreased activity and motor dysfunction.
Dopamine injections temporarily restored movement.
How did MPTP-treated monkeys behave compared to controls?
Control monkeys: Normal circadian movement — active periods and rest cycles.
MPTP monkeys: Severe reduction in movement.
Only active during dopamine administration.
Loss of substantia nigra neurons confirmed histologically.
How was rotenone used to investigate pesticide exposure and Parkinson’s?
Epidemiological links: farmers exposed to pesticides had higher Parkinson’s incidence.
Rotenone (a pesticide) was fed to transgenic fruit flies expressing green fluorescent dopaminergic neurons.
Dopaminergic neuron clusters degenerated after exposure.
Locomotor deficits confirmed by simple climbing assay (flies failed to ascend chambers).
What does rotenone exposure in flies show about Parkinson’s pathology?
Dopaminergic neuron degeneration is dose-dependent.
Locomotor impairment parallels human symptoms.
Suggests environmental toxins like rotenone can cause Parkinson’s via selective dopaminergic toxicity.
What are Lewy bodies and what proteins are they composed of?
Intracellular inclusions found in dying neurons in Parkinson’s disease.
Composed primarily of alpha-synuclein and ubiquitin.
Alpha-synuclein forms filamentous aggregates.
Ubiquitin tags indicate failed degradation attempts via the ubiquitin-proteasome system (UPS).
Why must researchers control for specificity in rotenone experiments?
Rotenone could non-specifically kill any neuron or cell type.
Control experiments must show selective dopaminergic neuron death.
Other neurons (e.g., cholinergic, GABAergic) must remain unaffected.
Ensures toxicity is relevant to Parkinson’s, not generalised cell death.
What does the presence of ubiquitin on Lewy bodies suggest?
Misfolded proteins are recognised and tagged for degradation.
However, degradation is not completed — proteins accumulate.
Implies dysfunction in the ubiquitin-proteasome system (UPS).
Supports the idea that defective protein clearance contributes to neuronal death.
What are the two main categories of causes for Parkinson’s disease?
Sporadic (unknown cause) — majority of cases.
Familial (genetic mutations) — minority of cases.
Some environmental factors are implicated in sporadic forms.
Which environmental toxin was linked to Parkinson’s via drug users?
MPTP – neurotoxin accidentally synthesized in drug preparation.
Causes irreversible Parkinsonian symptoms.
Selectively targets substantia nigra neurons.
Which genetic mutations are associated with juvenile-onset Parkinson’s disease?
Mutations in PINK1, Parkin, and DJ-1.
All are autosomal recessive.
Requires two copies of the mutated gene for disease expression.
Cause early (juvenile) or early-onset forms of Parkinson’s.
What do the autosomal recessive mutations in Parkin, PINK1, and DJ-1 imply about their function?
Suggest a loss-of-function mechanism.
One functional allele is sufficient for normal function.
Complete loss leads to disease.
Indicates their normal role is protective in neurons.
How is oxidative stress linked to Parkinson’s pathogenesis?
MPTP inhibits mitochondrial complex I → increased ROS.
DJ-1 protects against free radical damage.
PINK1 localises to mitochondria, suggesting a role in mitochondrial quality control.
Loss of these functions leads to accumulation of oxidative damage.
What experiment supports oxidative stress as a pathogenic mechanism?
Animals exposed to MPTP or rotenone show increased oxidative stress markers.
Free radical probes confirm ROS presence in substantia nigra.
Antioxidant treatment (e.g., in DJ-1 mutant models) reduces damage.
Suggests ROS is causally linked to neuron death.
