Long-term perampanel treatment in A53T BAC-SNCA mice with PFF injection

Validation Score: 0.950 Price: $0.50 Lewy body disease A53T BAC-SNCA transgenic mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting SNCA in A53T BAC-SNCA transgenic mice. Primary outcome: α-synuclein pathology spread and neurodegeneration

Description

This comprehensive experiment evaluated the disease-modifying potential of perampanel in A53T BAC-SNCA transgenic mice injected with PFFs. Mice received PFF injections followed by either perampanel or vehicle treatment for 2 and 9 months after PFF removal. The study assessed α-synuclein pathology spreading from first-order injection sites to second- and higher-order brain regions, as well as neurodegeneration. This experiment directly tests whether perampanel can prevent transsynaptic propagation of α-synuclein pathology and associated neuronal loss.

TARGET GENE
MODEL SYSTEM
A53T BAC-SNCA transgenic mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
protein aggregation, transsynaptic propagation, neurodegeneration
SOURCE
extracted_from_pmid_41508763
PRIMARY OUTCOME
α-synuclein pathology spread and neurodegeneration

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.950 composite

📖 Wiki Pages

snca-proteinproteinSNCA→Alpha-synuclein→Aggregation→Lewy Bodies→SynucpathwaySNCA — Alpha-SynucleingeneSNCA Gene Variants and MutationsdiseaseSNCA A53TdiseaseSNCA-Overexpressing Dopaminergic NeuronscellSNCA-A53T Alpha-Synuclein NeuronscellA53T Alpha-Synuclein Transgenic Mouse Model of ParmodelSNCA→Alpha-synuclein→Parkinson's Disease Causal ChpathwaySNCA — Alpha-Synuclein Gene Entity PagegeneNeurodegenerationdiseaseBrain Regionsindex

Protocol

PFF injection followed by perampanel or vehicle treatment for 2 and 9 months, with assessment of pathology in different brain regions

Expected Outcomes

reduced α-synuclein pathology in distant regions and ameliorated neurodegeneration with perampanel treatment

Success Criteria

significant reduction in pathology spread to second/higher-order regions and reduced neurodegeneration

Related Hypotheses (1)

Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization0.382

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