Parkinson’s Disease-linked protein α-synuclein: do small-molecule inhibitors of protein aggregation also prevent its accumulation with lipids?
Bibliographic record
Abstract
Parkinson’s Disease (PD), a neurodegenerative disorder, is characterized by the pathological aggregation of α-synuclein (αS) into Lewy bodies, primarily composed of fibrillar and lipid/membrane-rich αS inclusions. Recent studies suggest that both fibrillar and lipid-rich αS aggregates may contribute to PD pathology. This study investigates how lipid-rich αS inclusions are affected by small molecules that had previously been shown to disaggregate fibrillar αS protein aggregation. Using a live-cellular assay based on YFP-tagged membrane - accumulating, engineered αS-3K (E35K+E46K+E61K) in M17D neuroblastoma cells, we assessed the effects of fasudil, Epigallocatechin gallate (EGCG), anle138b, and ethanol compared to the positive control trifluoperazine (TFP), which is known to disassemble lipid-rich αS aggregates. fasudil, EGCG, and anle138b had previously been shown to prevent protein aggregation of αS. In our experiments, fasudil and anle138b significantly decreased inclusion formation in a dose - dependent manner in both αS lipid-rich inclusion prevention and reduction assays, while EGCG and ethanol exhibited either negligible or inclusion-increasing effects. These findings indicate that fasudil and anle138b may effectively target lipid-rich αS inclusions, supporting further exploration of their therapeutic potential in PD. However, fasudil’s observed associated toxicity necessitates careful evaluation. This study underscores the therapeutic relevance of targeting diverse αS aggregate types in PD.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".