The Reversal Initiative

10 Curated Targets.
Complete AI Workflows.

A curated set of Alzheimer's disease targets spanning NAD+ metabolism, amyloid, tau, lipid homeostasis, neuroinflammation, and RNA splicing. Each target paired with production-ready AI analysis pipelines.

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Target Library

10 Curated Alzheimer's Targets

Each target selected based on genetic evidence, druggability assessment, and potential for disease modification. Color-coded by biological pathway.

NAMPT
NAMPT / PBEF1
NAD+ Metabolism
Nicotinamide phosphoribosyltransferase. Rate-limiting enzyme in NAD+ salvage pathway. NAD+ depletion drives neuronal vulnerability in AD. Small-molecule activators restore NAD+ levels.
NMNAT2
NMNAT2
NAD+ Metabolism
Nicotinamide mononucleotide adenylyltransferase 2. Neuronal-specific NAD+ synthesizing enzyme. Depletion precedes axonal degeneration. Stabilizers protect against Wallerian degeneration.
BACE1
BACE1
Amyloid
Beta-secretase 1. Initiates amyloidogenic processing of APP. Inhibitors reduce amyloid-beta production. Next-gen approaches target substrate selectivity to reduce mechanism-based toxicity.
γ-Secretase
PSEN1 / PSEN2
Amyloid
Presenilin-containing gamma-secretase complex. Cleaves APP to generate A-beta 40/42. Modulators shift cleavage to shorter, less toxic peptides without complete inhibition.
GSK-3β
GSK3B
Tau
Glycogen synthase kinase 3 beta. Primary kinase for tau hyperphosphorylation. Inhibitors reduce neurofibrillary tangle formation. Selectivity over GSK-3-alpha critical for safety.
CDK5/p25
CDK5
Tau
Cyclin-dependent kinase 5 with p25 activator. Aberrant CDK5/p25 drives tau phosphorylation and neuronal death. Disrupting p25 binding without blocking p35 preserves normal function.
IDOL
MYLIP
Lipid
Inducible degrader of the LDL receptor. E3 ubiquitin ligase controlling cholesterol uptake. Brain cholesterol homeostasis disrupted in AD. Inhibitors restore neuronal lipid metabolism.
TREM2
TREM2
Inflammation
Triggering receptor expressed on myeloid cells 2. Microglial receptor for amyloid-beta clearance. R47H variant confers 3x AD risk. Agonist antibodies enhance microglial phagocytosis.
NLRP3
NLRP3
Inflammation
NOD-like receptor protein 3 inflammasome. Drives IL-1-beta and IL-18 release in neuroinflammation. A-beta activates NLRP3. Inhibitors reduce neuroinflammation and tau pathology.
EVA1C
EVA1C / C21orf63
RNA Splicing
Eva-1 homolog C. Recently identified GWAS hit linked to AD risk. Involved in RNA splicing regulation in neurons. Novel target with emerging biology and high druggability potential.
Capabilities

What the Toolbox Can Do

Every target in our Alzheimer's library comes with pre-configured analysis pipelines covering the full computational drug discovery workflow.

Structure Prediction

AlphaFold2/ESMFoldAI structure prediction modeling for each target. Pre-computed structures ready for docking.

Virtual Screening

AutoDock VinaVirtual screening campaigns against curated compound libraries. Hit identification and binding mode analysis.

Stability Engineering

FoldXStability analysis mutation scanning for protein stabilization. Identify mutations improving expression and thermal stability.

De Novo Generation

Active-learning molecular generation optimized for each target's binding site topology.

ADMET Profiling

Multi-endpoint toxicology prediction. BBB permeability scoring critical for CNS drug candidates.

Report Generation

Automated ICH-aligned reporting with forensic verification. Regulatory-ready documentation.

The Reversal Initiative

Join the Mission. Fund the Research.

The Reversal Initiative is our open research program targeting Alzheimer's disease. We believe computational drug discovery can accelerate the path to disease-modifying treatments. Support our work on these 10 targets.

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An AIXC Research Project

Explore Our Full Platform

The Alzheimer's Toolbox runs on 37+ production modules. See the complete platform capabilities.

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