Protein Drug Targets

Protein Drug Targets

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Protein Drug Targets</th>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">BACE1</td>
<td>[Beta-secretase](/entities/bace1)</td>
</tr>
<tr>
<td class="label">[Gamma-secretase](/entities/gamma-secretase)</td>
<td>[PSEN1](/entities/psen1)/2 complex</td>
</tr>
<tr>
<td class="label">[Amyloid-beta](/proteins/amyloid-beta)</td>
<td>Aβ aggregation</td>
</tr>
<tr>
<td class="label">Amyloid-beta</td>
<td>Aβ production</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">Tau kinases</td>
<td>GSK3β, [CDK5](/proteins/cdk5)</td>
</tr>
<tr>
<td class="label">Tau aggregation</td>
<td>[MAPT](/proteins/tau)</td>
</tr>
<tr>
<td class="label">Tau</td>
<td>Tau clearance</td>
</tr>
<tr>
<td class="label">Tau</td>
<td>Tau clearance</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">AChE</td>
<td>Acetylcholinesterase</td>
</tr>
<tr>
<td class="label">[NMDA receptor](/entities/nmda-receptor)</td>
<td>GRIN1/2</td>
</tr>
<tr>
<td class="label">Muscarinic receptor</td>
<td>CHRM1, CHRM3</td>
</tr>
<tr>
<td class="label">5-HT receptor</td>
<td>HTR2A, HTR6</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">[TREM2](/proteins/tr

Protein Drug Targets

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Protein Drug Targets</th>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">BACE1</td>
<td>[Beta-secretase](/entities/bace1)</td>
</tr>
<tr>
<td class="label">[Gamma-secretase](/entities/gamma-secretase)</td>
<td>[PSEN1](/entities/psen1)/2 complex</td>
</tr>
<tr>
<td class="label">[Amyloid-beta](/proteins/amyloid-beta)</td>
<td>Aβ aggregation</td>
</tr>
<tr>
<td class="label">Amyloid-beta</td>
<td>Aβ production</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">Tau kinases</td>
<td>GSK3β, [CDK5](/proteins/cdk5)</td>
</tr>
<tr>
<td class="label">Tau aggregation</td>
<td>[MAPT](/proteins/tau)</td>
</tr>
<tr>
<td class="label">Tau</td>
<td>Tau clearance</td>
</tr>
<tr>
<td class="label">Tau</td>
<td>Tau clearance</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">AChE</td>
<td>Acetylcholinesterase</td>
</tr>
<tr>
<td class="label">[NMDA receptor](/entities/nmda-receptor)</td>
<td>GRIN1/2</td>
</tr>
<tr>
<td class="label">Muscarinic receptor</td>
<td>CHRM1, CHRM3</td>
</tr>
<tr>
<td class="label">5-HT receptor</td>
<td>HTR2A, HTR6</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">[TREM2](/proteins/trem2)</td>
<td>TREM2</td>
</tr>
<tr>
<td class="label">CD33</td>
<td>CD33</td>
</tr>
<tr>
<td class="label">NLRP3</td>
<td>[NLRP3 inflammasome](/entities/nlrp3-inflammasome)</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">[Alpha-synuclein](/proteins/alpha-synuclein)</td>
<td>SNCA</td>
</tr>
<tr>
<td class="label">Alpha-synuclein</td>
<td>SNCA</td>
</tr>
<tr>
<td class="label">Alpha-synuclein</td>
<td>SNCA</td>
</tr>
<tr>
<td class="label">GBA</td>
<td>Glucocerebrosidase</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">D2 receptor</td>
<td>DRD2</td>
</tr>
<tr>
<td class="label">MAO-B</td>
<td>MAO-B</td>
</tr>
<tr>
<td class="label">COMT</td>
<td>COMT</td>
</tr>
<tr>
<td class="label">A2A receptor</td>
<td>ADORA2A</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">LRRK2 kinase</td>
<td>LRRK2</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">SOD1</td>
<td>Superoxide dismutase 1</td>
</tr>
<tr>
<td class="label">SOD1</td>
<td>SOD1</td>
</tr>
<tr>
<td class="label">[C9orf72](/entities/c9orf72)</td>
<td>C9orf72</td>
</tr>
<tr>
<td class="label">FUS</td>
<td>FUS</td>
</tr>
<tr>
<td class="label">ATXN2</td>
<td>Ataxin-2</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">NMDA receptor</td>
<td>GRIN1/2</td>
</tr>
<tr>
<td class="label">AMPA receptor</td>
<td>GRIA1-4</td>
</tr>
<tr>
<td class="label">Cytosolic [ROS](/entities/reactive-oxygen-species)</td>
<td>SOD1</td>
</tr>
</table>

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. [@alzheimers2024]

Drug targets in neurodegenerative diseases span multiple categories: proteins involved in disease pathogenesis, proteins regulating protein homeostasis, and proteins modulating cellular survival pathways. [@parkinsons2023]

--- [@als2023]

Alzheimer's Disease Drug Targets

Amyloid Pathway Targets

Tau Pathway Targets

Neurotransmission Targets

Neuroinflammation Targets

Parkinson's Disease Drug Targets

Alpha-Synuclein Targets

Dopamine Pathway Targets

LRRK2 Targets

ALS Drug Targets

Genetic Target Approaches

Neuroprotection Targets

Target Validation Considerations

Genetic Validation

• GWAS hits provide human genetic validation
• Mendelian mutations provide causal evidence
• Polygenic scores can identify additive targets

Preclinical Validation

• Knockout/knockin mouse models
• In vitro assays using patient-derived cells
• iPSC neuronal models

Clinical Validation

• Biomarker engagement studies
• Target occupancy measurements
• Mechanistic biomarker readouts

Emerging Target Categories

Protein Homeostasis

• [Autophagy](/entities/autophagy) enhancers
• Proteasome modulators
• Molecular chaperones

Cellular Rejuvenation

• Senolytics
• Cellular reprogramming factors
• Youth factors (e.g., Klotho)

RNA Targets

• RNA-binding proteins
• Long non-coding RNAs
• MicroRNAs

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References