🧪
hypothesis

Sphingolipid Metabolism Rebalancing

Hypothesis

Sphingolipid Metabolism Rebalancing

Target sphingomyelin phosphodiesterase or ceramide kinase to restore membrane fluidity and improve phagocytic function through membrane composition optimization.
🧬 SMPD1🩺 neurodegeneration🎯 Composite 46%💱 $0.52▲5.7%active
EvidencePending (0%)📖 5 cit🗣 1 debates 5 support 3 oppose
✓ All Quality Gates Passed
Mechanistic 0.50 (15%) Evidence 0.50 (15%) Novelty 0.50 (12%) Feasibility 0.50 (12%) Impact 0.00 (12%) Druggability 0.50 (10%) Safety 0.50 (8%) Competition 0.50 (6%) Data Avail. 0.50 (5%) Reproducible 0.50 (5%) KG Connect 0.50 (8%) 0.455 composite
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arXiv PreprintNeurIPSNature MethodsPLOS ONE
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Composite46%

🧪 Overview

Target sphingomyelin phosphodiesterase or ceramide kinase to restore membrane fluidity and improve phagocytic function through membrane composition optimization

🧬 Mechanism

🔗 Mechanism from KG for SMPD1

Auto-built from this analysis's top knowledge-graph edges.

graph TD
    NAD__biosynthesis["NAD+ biosynthesis"] -->|activates| sirtuin_function["sirtuin function"]
    TREM2["TREM2"] -->|mediates| amyloid_clearance["amyloid clearance"]
    NAMPT["NAMPT"] -->|associated with| Nad__Biosynthesis["Nad+ Biosynthesis"]
    Nad__Biosynthesis_1["Nad+ Biosynthesis"] -->|associated with| sirtuin_function_2["sirtuin function"]
    apoe4["apoe4"] -->|causes| metabolic_crisis["metabolic crisis"]
    APOE4["APOE4"] -.->|inhibits| NAMPT_3["NAMPT"]
    APOE4_4["APOE4"] -->|activates| MTOR_signaling["MTOR signaling"]
    MTOR["MTOR"] -->|regulates| metabolic_flexibility["metabolic flexibility"]
    APOE4_5["APOE4"] -->|causes| lipid_droplet_formation["lipid droplet formation"]
    DGAT1["DGAT1"] -->|catalyzes| lipid_droplet_formation_6["lipid droplet formation"]
    APOE4_7["APOE4"] -->|disrupts| mitochondrial_ER_contacts["mitochondrial-ER contacts"]
    VDAC1["VDAC1"] -->|regulates| mitochondrial_ER_contacts_8["mitochondrial-ER contacts"]
    style NAD__biosynthesis fill:#81c784,stroke:#333,color:#000
    style sirtuin_function fill:#4fc3f7,stroke:#333,color:#000
    style TREM2 fill:#4fc3f7,stroke:#333,color:#000
    style amyloid_clearance fill:#4fc3f7,stroke:#333,color:#000
    style NAMPT fill:#ce93d8,stroke:#333,color:#000
    style Nad__Biosynthesis fill:#81c784,stroke:#333,color:#000
    style Nad__Biosynthesis_1 fill:#81c784,stroke:#333,color:#000
    style sirtuin_function_2 fill:#4fc3f7,stroke:#333,color:#000
    style apoe4 fill:#ef5350,stroke:#333,color:#000
    style metabolic_crisis fill:#4fc3f7,stroke:#333,color:#000
    style APOE4 fill:#ce93d8,stroke:#333,color:#000
    style NAMPT_3 fill:#ce93d8,stroke:#333,color:#000
    style APOE4_4 fill:#ce93d8,stroke:#333,color:#000
    style MTOR_signaling fill:#81c784,stroke:#333,color:#000
    style MTOR fill:#4fc3f7,stroke:#333,color:#000
    style metabolic_flexibility fill:#4fc3f7,stroke:#333,color:#000
    style APOE4_5 fill:#ce93d8,stroke:#333,color:#000
    style lipid_droplet_formation fill:#4fc3f7,stroke:#333,color:#000
    style DGAT1 fill:#4fc3f7,stroke:#333,color:#000
    style lipid_droplet_formation_6 fill:#4fc3f7,stroke:#333,color:#000
    style APOE4_7 fill:#ce93d8,stroke:#333,color:#000
    style mitochondrial_ER_contacts fill:#4fc3f7,stroke:#333,color:#000
    style VDAC1 fill:#4fc3f7,stroke:#333,color:#000
    style mitochondrial_ER_contacts_8 fill:#4fc3f7,stroke:#333,color:#000

⚖️ Evidence

⚖️ Evidence Matrix5 supports3 contradicts
Supports
Targeting glioblastoma signaling and metabolism with a re-purposed brain-penetrant drug.
Cell Rep2021PMID:34731610medium
Supports
The Niemann-Pick type diseases - A synopsis of inborn errors in sphingolipid and cholesterol metabolism.
Prog Lipid Res2023PMID:37003582medium
Supports
Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.
Hum Mutat2021PMID:33675270medium
Supports
EDIL3/Del-1 prevents aortic dissection through enhancing internalization and degradation of apoptotic vascular smooth muscle cells.
Autophagy2024PMID:38873925medium
Supports
The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review.
Biomolecules2024PMID:38397448medium
Contradicts
The Niemann-Pick type diseases - A synopsis of inborn errors in sphingolipid and cholesterol metabolism.
Prog Lipid Res2023PMID:37003582medium
Contradicts
Linking autism spectrum disorders and parkinsonism: clinical and genetic association.
Ann Clin Transl Neurol2023PMID:36738194medium
Contradicts
Acid sphingomyelinase as a pathological and therapeutic target in neurological disorders: focus on Alzheimer's disease.
Exp Mol Med2024PMID:38337058medium
📖 Linked Papers

No linked papers recorded for this hypothesis yet.

🏥 Translation

🧬 3D Protein Structure — SMPD1

🧬 PDB 5I73 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

💉 Clinical Trials

No clinical trials data linked to this hypothesis yet.

No curated ClinVar variants loaded for this hypothesis.

Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.

🔍 Search ClinVar for SMPD1 →

No DepMap CRISPR Chronos data found for SMPD1.

Run python3 scripts/backfill_hypothesis_depmap.py to populate.

🏆 Tournament

🏆 Arenas / Elo

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📊 Market Indicators

7d Trend
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0527
Events (7d)
0
Price History
▲5.7%

💾 Resource Usage

LLM Tokens
12,984
$0.0779
Total Cost
$0.0779
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