Screening models for anti-Parkinson’s drugs provide essential preclinical platforms to evaluate efficacy, safety and mechanisms of candidate compounds. B. Pharm students should master in vitro systems (SH-SY5Y, PC12), primary mesencephalic cultures, and in vivo toxin (6‑OHDA, MPTP, rotenone) and genetic (alpha‑synuclein, LRRK2, Parkin) models used to assess neuroprotection, dopaminergic neuron loss, motor deficits and biomarkers. Key readouts include behavioral assays (rotarod, pole test, apomorphine rotations), biochemical measures (striatal dopamine, TH immunostaining, oxidative stress markers) and screening strategies (high‑throughput, phenotypic vs target‑based). Understanding advantages, limitations and translational considerations is vital for anti‑Parkinson’s drug discovery. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary purpose of preclinical screening models for anti‑Parkinson’s drugs?
- To determine marketing strategies for new drugs
- To evaluate efficacy, safety and mechanism of candidate compounds
- To replace clinical trials entirely
- To test cosmetic effects of compounds
Correct Answer: To evaluate efficacy, safety and mechanism of candidate compounds
Q2. Which human neuroblastoma cell line is commonly used as an in vitro dopaminergic model in Parkinson’s research?
- HEK293
- SH-SY5Y
- COS-7
- CHO
Correct Answer: SH-SY5Y
Q3. Which neurotoxin is commonly injected unilaterally into the medial forebrain bundle or striatum to create a rodent model of Parkinsonism?
- Paraquat
- Rotenone
- 6‑Hydroxydopamine (6‑OHDA)
- Dopamine
Correct Answer: 6‑Hydroxydopamine (6‑OHDA)
Q4. Which compound produces Parkinson-like lesions after systemic administration in mice and primates by targeting dopaminergic neurons?
- MPTP
- L-DOPA
- Reserpine
- Carbidopa
Correct Answer: MPTP
Q5. The rotarod test in rodent screening models primarily evaluates which endpoint?
- Cognitive flexibility
- Sensory acuity
- Motor coordination and balance
- Sleep pattern
Correct Answer: Motor coordination and balance
Q6. Apomorphine‑induced rotation test is used in unilateral lesion models to assess what?
- Gastrointestinal motility
- Functional asymmetry of the nigrostriatal pathway
- Renal clearance of drugs
- Cardiac output changes
Correct Answer: Functional asymmetry of the nigrostriatal pathway
Q7. Which immunohistochemical marker is most widely used to identify dopaminergic neurons in screening studies?
- GFAP
- Tyrosine hydroxylase (TH)
- NeuN
- S100β
Correct Answer: Tyrosine hydroxylase (TH)
Q8. Which in vitro assay measures cell viability by mitochondrial dehydrogenase activity commonly used in neurotoxicity screens?
- ELISA
- MTT assay
- Western blot
- TUNEL assay
Correct Answer: MTT assay
Q9. Rotenone induces Parkinson-like pathology by inhibiting which mitochondrial complex?
- Complex II
- Complex I
- Complex III
- ATP synthase (Complex V)
Correct Answer: Complex I
Q10. A key advantage of high‑content screening (HCS) for anti‑Parkinson’s discovery is:
- It only measures a single biochemical parameter
- It provides multiplexed phenotypic cellular readouts
- It eliminates the need for animal models entirely
- It is unsuitable for neuronal cells
Correct Answer: It provides multiplexed phenotypic cellular readouts
Q11. Mutations in which gene are commonly modeled in transgenic animals to study familial Parkinson’s disease?
- APP
- LRRK2
- CFTR
- BRCA1
Correct Answer: LRRK2
Q12. Which biochemical marker indicates lipid peroxidation and oxidative stress in PD models?
- Glutathione peroxidase activity only
- Malondialdehyde (MDA) levels
- Acetylcholine levels
- Albumin concentration
Correct Answer: Malondialdehyde (MDA) levels
Q13. Which rodent model is widely used to test neuroprotective agents because it produces relatively selective nigrostriatal lesions?
- Kainic acid hippocampal model
- 6‑OHDA rat model
- Streptozotocin diabetic model
- CCI neuropathic pain model
Correct Answer: 6‑OHDA rat model
Q14. A major limitation of many toxin‑based Parkinson’s models is:
- They perfectly reproduce human disease progression
- They do not model progressive, multifactorial human PD accurately
- They are too slow to generate lesions
- They cannot be combined with behavioral assays
Correct Answer: They do not model progressive, multifactorial human PD accurately
Q15. Overexpression of alpha‑synuclein in transgenic models primarily helps study:
- Peripheral immune responses
- Protein aggregation and Lewy body‑like pathology
- Cardiac arrhythmias
- Renal toxicity
Correct Answer: Protein aggregation and Lewy body‑like pathology
Q16. Which neurotransmitter is characteristically depleted in the striatum in Parkinson’s disease models?
- Acetylcholine
- Serotonin
- Dopamine
- GABA
Correct Answer: Dopamine
Q17. In drug screening for Parkinson’s, inhibition of which enzyme is a therapeutic strategy to increase synaptic dopamine?
- COMT only
- Monoamine oxidase B (MAO‑B)
- AChE
- Tyrosine hydroxylase
Correct Answer: Monoamine oxidase B (MAO‑B)
Q18. Which behavioral test is sensitive to bradykinesia and akinesia in rodent Parkinson’s models?
- Forced swim test
- Pole test
- Morris water maze
- Tail suspension test
Correct Answer: Pole test
Q19. The gold‑standard analytical technique for quantifying striatal dopamine and its metabolites in screening studies is:
- Colorimetric assay
- HPLC with electrochemical detection (HPLC‑ECD)
- ELISA for dopamine
- Immunofluorescence only
Correct Answer: HPLC with electrochemical detection (HPLC‑ECD)
Q20. Which compound, when administered systemically to mice, reliably produces nigrostriatal degeneration resembling Parkinsonism?
- Loratadine
- MPTP
- Diazepam
- Imatinib
Correct Answer: MPTP
Q21. Which compound is commonly used in vitro to induce mitochondrial dysfunction in dopaminergic cell models?
- Rotenone
- Ibuprofen
- Penicillin
- Metformin
Correct Answer: Rotenone
Q22. Using a battery of behavioral tests in preclinical screening helps to:
- Assess only cognitive effects
- Differentiate symptomatic relief from disease‑modifying neuroprotection
- Eliminate the need for biochemical endpoints
- Measure kidney function
Correct Answer: Differentiate symptomatic relief from disease‑modifying neuroprotection
Q23. The dopamine transporter (DAT) primarily functions to:
- Synthesize dopamine from tyrosine
- Reuptake dopamine from the synaptic cleft
- Metabolize dopamine to DOPAC
- Transport dopamine into vesicles
Correct Answer: Reuptake dopamine from the synaptic cleft
Q24. Which finding is a key indicator of a successful 6‑OHDA lesion in nigrostriatal models?
- Increased striatal TH staining
- Loss of TH‑positive neurons in substantia nigra pars compacta
- Enhanced hippocampal neurogenesis
- Improved motor coordination
Correct Answer: Loss of TH‑positive neurons in substantia nigra pars compacta
Q25. Which assay specifically detects DNA fragmentation as a marker of apoptosis in neuronal cultures?
- TUNEL assay
- MTT assay
- Western blot for actin
- HPLC
Correct Answer: TUNEL assay
Q26. For producing a rapid and robust nigrostriatal lesion in rats, 6‑OHDA is often injected stereotaxically into which site?
- Medial forebrain bundle (MFB)
- Cerebellum
- Prefrontal cortex
- Hippocampus
Correct Answer: Medial forebrain bundle (MFB)
Q27. An important advantage of cell‑based high‑throughput screens in anti‑Parkinson’s discovery is:
- They are always predictive of human efficacy
- They allow rapid, cost‑effective testing of large compound libraries
- They do not require assay validation
- They measure whole‑animal behavior
Correct Answer: They allow rapid, cost‑effective testing of large compound libraries
Q28. Activation of microglia in Parkinson’s models is commonly assessed by measuring which marker?
- Iba1 expression
- Albumin levels
- Myelin basic protein
- Insulin receptor
Correct Answer: Iba1 expression
Q29. Which combination of outcomes in a preclinical model best supports that a test compound is neuroprotective?
- Reduced body weight and increased anxiety
- Preservation of TH‑positive neurons and improved motor behavior
- Increased liver enzymes only
- Enhanced rotarod deficits with no biochemical change
Correct Answer: Preservation of TH‑positive neurons and improved motor behavior
Q30. A frequent reason for failure to translate preclinical anti‑Parkinson’s successes to the clinic is:
- Perfect modelling of human Parkinson’s in animals
- Species differences and incomplete recapitulation of human disease complexity
- Excessively long clinical trials
- Too many biomarkers in preclinical studies
Correct Answer: Species differences and incomplete recapitulation of human disease complexity
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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