This page ranks proteins associated with neurodegenerative diseases by various criteria including disease relevance, research activity, therapeutic target validation, and knowledge base coverage in NeuroWiki. [1]
| Rank | Protein | Function | Research Activity | [2]
|------|---------|----------|-------------------| [3]
| 1 | Amyloid-beta (Aβ) | Amyloid plaque formation | Very High |
| 2 | Tau (MAPT) | Neurofibrillary tangles | Very High |
| 3 | APP | Amyloid precursor protein | Very High |
| 4 | TREM2 | Microglial receptor | Very High |
| 5 | APOE | Lipid transport | Very High |
| 6 | BACE1 | Beta-secretase | High |
| 7 | Clusterin | Amyloid clearance | High |
| 8 | GFAP | Astrocyte marker | High |
| 9 | Neurofilament light chain (NfL) | Neurodegeneration marker | Very High |
| 10 | Synaptic proteins | Synaptic function | High |
| Rank | Protein | Function | Research Activity |
|---|---|---|---|
| 1 | Alpha-synuclein | Lewy body formation | Very High |
| 2 | LRRK2 | Leucine-rich repeat kinase | Very High |
| 3 | GCase (GBA) | Lysosomal enzyme | Very High |
| 4 | Parkin | Mitophagy | High |
| 5 | PINK1 | Mitophagy | High |
| 6 | DJ-1 | Oxidative stress | Moderate-High |
| 7 | VPS35 | Endosomal trafficking | Moderate-High |
| 8 | Synphilin-1 | Alpha-synuclein aggregation | Moderate |
| 9 | GSN (Gelsolin) | Actin remodeling | Moderate |
| 10 | ATP13A2 (PARK9) | Lysosomal function | Moderate |
| Rank | Protein | Function | Research Activity |
|---|---|---|---|
| 1 | TDP-43 | RNA metabolism | Very High |
| 2 | FUS | RNA metabolism | Very High |
| 3 | SOD1 | Superoxide dismutase | Very High |
| 4 | C9orf72 protein | RNA binding | Very High |
| 5 | OPTN | Autophagy receptor | High |
| 6 | TBK1 | Kinase, autophagy | High |
| 7 | VCP/ALS4 | Protein degradation | Moderate-High |
| 8 | Ubiquilin-2 | Protein degradation | Moderate |
| 9 | Peripherin | Intermediate filament | Moderate |
| 10 | Astrocytic proteins | Astrocyte response | Moderate |
Proteins with strong evidence for therapeutic targeting:
| Rank | Protein | Target Approach | Development Stage |
|---|---|---|---|
| 1 | Amyloid-beta | Immunotherapy (lecanemab, donanemab) | Approved/Phase 3 |
| 2 | Tau | Immunotherapy (gosuranemab, semorinemab) | Phase 2-3 |
| 3 | Alpha-synuclein | Immunotherapy (prasinezumab) | Phase 2 |
| 4 | TREM2 | Agonist antibodies | Phase 1-2 |
| 5 | LRRK2 | Kinase inhibitors (DNL151) | Phase 1-2 |
| 6 | SOD1 | Gene therapy, ASO | Phase 1-2 |
| 7 | GCase | Small molecule chaperones | Phase 1-2 |
| 8 | BACE1 | Inhibitors (halted due to safety) | Phase 3 |
These ranked items have limited content and would benefit from expansion:
These items are listed in rankings but have no corresponding wiki page:
Amyloid-beta immunotherapy. N Engl J Med. 2023. ↩︎
Alpha-synuclein and Parkinson's disease. Nat Rev Dis Primers. 2019. ↩︎
TDP-43 proteinopathies. Nat Rev Neurol. 2010. ↩︎