PFF uptake in primary hippocampal neurons with inhibitors

Exploratory Score: 0.900 Price: $0.50 Lewy body disease mouse primary hippocampal neurons Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting SNCA in mouse primary hippocampal neurons. Primary outcome: neuronal uptake of PFFs

Description

This experiment examined the mechanisms of neuronal uptake of α-synuclein preformed fibrils (PFFs) in primary hippocampal neurons. PFFs were labeled with pH-sensitive dye to track uptake. Neurons were treated with either dynamin inhibitors or clathrin inhibitors to determine which endocytic pathway is responsible for PFF uptake. The study aimed to understand whether PFF uptake occurs through clathrin-mediated endocytosis or dynamin-dependent mechanisms.

TARGET GENE
MODEL SYSTEM
mouse primary hippocampal neurons
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
endocytosis, protein aggregation
SOURCE
extracted_from_pmid_41508763
PRIMARY OUTCOME
neuronal uptake of PFFs

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%) 0.900 composite

📖 Wiki Pages

NCT04724941: Prodromal Alpha-Synuclein ScreeningmechanismSNCA-A53T Alpha-Synuclein NeuronscellSNCA-Overexpressing Dopaminergic NeuronscellSNCA A53TdiseaseSNCA Gene Variants and MutationsdiseaseSNCA — Alpha-Synuclein Gene Entity PagegeneSNCA — Alpha-Synucleingenesnca-proteinproteinSNCA→Alpha-synuclein→Aggregation→Lewy Bodies→SynucpathwaySNCA→Alpha-synuclein→Parkinson's Disease Causal ChpathwayMechanismsindexHippocampal Neuronscell

Protocol

PFFs labeled with pH-sensitive dye were applied to cultured neurons, with treatment using dynamin or clathrin inhibitors

Expected Outcomes

PFF uptake would be blocked by dynamin inhibitors but not clathrin inhibitors

Success Criteria

significant reduction in PFF uptake with dynamin inhibition

Related Hypotheses (6)

Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization0.571
Exosomal SNCA Propagation from Lysosome-Compromised Neurons Contains a Distinct Lysosomal Proteome S0.777
SNCA Aggregation Hijacks the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery via 0.690
m6A Hypermethylation of SNCA mRNA Stabilises Alpha-Synuclein Transcript and Promotes Lewy Pathology0.662
Physiological SCFAs may reduce alpha-synuclein burden primarily through a gut-first or ENS-first mec0.650

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