This page catalogs proteins that serve as direct or indirect targets for drug development in neurodegenerative diseases. Understanding drug target prioritization helps identify promising therapeutic approaches and track the drug development pipeline.
Drug targets in neurodegenerative diseases span multiple categories: proteins involved in disease pathogenesis, proteins regulating protein homeostasis, and proteins modulating cellular survival pathways.
---
| Target | Protein | Drug Type | Development Stage | Examples |
|--------|---------|-----------|------------------|----------|
| BACE1 | Beta-secretase | Small molecule | Failed | Verubecestat, Lanabecestat |
| Gamma-secretase | PSEN1/2 complex | Small molecule | Failed | Semagacestat |
| Amyloid-beta | Aβ aggregation | Immunotherapy | Approved/Phase III | Aducanumab, Lecanemab, Donanemab |
| Amyloid-beta | Aβ production | Immunotherapy | Phase II | ACI-35 (liposome vaccine) |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| Tau kinases |
GSK3β, CDK5 |
Small molecule |
Research |
Tideglusib |
| Tau aggregation |
MAPT |
Small molecule |
Phase II |
Methylthioninium chloride |
| Tau |
Tau clearance |
Immunotherapy |
Phase II |
Gosuranemab, Semorinemab |
| Tau |
Tau clearance |
ASO |
Preclinical |
Antisense oligonucleotides |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| AChE |
Acetylcholinesterase |
Small molecule |
Approved |
Donepezil, Rivastigmine, Galantamine |
| NMDA receptor |
GRIN1/2 |
Small molecule |
Approved |
Memantine |
| Muscarinic receptor |
CHRM1, CHRM3 |
Small molecule |
Phase II |
Xanomeline |
| 5-HT receptor |
HTR2A, HTR6 |
Small molecule |
Phase II |
Pimavanserin |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| TREM2 |
TREM2 |
Antibody |
Phase II |
AL002 |
| CD33 |
CD33 |
Antibody |
Preclinical |
Rituximab (repurposed) |
| NLRP3 |
NLRP3 inflammasome |
Small molecule |
Research |
MCC950 |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| Alpha-synuclein |
SNCA |
Immunotherapy |
Phase II |
Cinpanemab, Prasinezumab |
| Alpha-synuclein |
SNCA |
ASO |
Preclinical |
ASO targeting SNCA |
| Alpha-synuclein |
SNCA |
Gene therapy |
Preclinical |
AAV-delivered shRNA |
| GBA |
Glucocerebrosidase |
Small molecule |
Phase II |
GZ161 |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| D2 receptor |
DRD2 |
Agonist |
Approved |
Pramipexole, Ropinirole |
| MAO-B |
MAO-B |
Inhibitor |
Approved |
Selegiline, Rasagiline |
| COMT |
COMT |
Inhibitor |
Approved |
Entacapone, Opicapone |
| A2A receptor |
ADORA2A |
Antagonist |
Phase III |
Istradefylline |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| LRRK2 kinase |
LRRK2 |
Small molecule |
Phase II |
DNL151, BBT287 |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| SOD1 |
Superoxide dismutase 1 |
ASO |
Approved |
Tofersen |
| SOD1 |
SOD1 |
Gene therapy |
Phase I/II |
AXON-101 |
| C9orf72 |
C9orf72 |
ASO |
Phase I/II |
WVE-004 |
| FUS |
FUS |
ASO |
Preclinical |
ASO targeting FUS |
| ATXN2 |
Ataxin-2 |
ASO |
Preclinical |
ASO targeting ATXN2 |
| Target |
Protein |
Drug Type |
Development Stage |
Examples |
| NMDA receptor |
GRIN1/2 |
Antagonist |
Approved |
Riluzole |
| AMPA receptor |
GRIA1-4 |
Modulator |
Phase III |
Perampanel |
| Cytosolic ROS |
SOD1 |
Gene therapy |
Approved |
Tofersen |
- GWAS hits provide human genetic validation
- Mendelian mutations provide causal evidence
- Polygenic scores can identify additive targets
- Knockout/knockin mouse models
- In vitro assays using patient-derived cells
- iPSC neuronal models
- Biomarker engagement studies
- Target occupancy measurements
- Mechanistic biomarker readouts
- Autophagy enhancers
- Proteasome modulators
- Molecular chaperones
- Senolytics
- Cellular reprogramming factors
- Youth factors (e.g., Klotho)
- RNA-binding proteins
- Long non-coding RNAs
- MicroRNAs