🎯 Drug Targets

Immunotherapy targeting alpha-synuclein aggregates or small molecules preventing aggregation

Small molecule stabilizers of microtubule structure or assembly

STX17-targeting drugs would enhance or modulate autophagosome-lysosome fusion by facilitating SNARE complex assembly, thereby improving autophagic clearance of misfolded proteins and damaged organelles. This mechanism is particularly relevant for neurodegenerative diseases characterized by protein aggregation.

Direct LAMP1 modulators enhance lysosomal membrane trafficking and autophagy flux, while indirect pathway drugs alter lysosomal pH and autophagosome-lysosome fusion dynamics to modulate LAMP1-mediated cellular clearance mechanisms.

Drugs targeting ZO1 typically work by stabilizing or modulating tight junction protein interactions, either by directly binding to ZO1 scaffolding domains or by regulating upstream signaling pathways that control ZO1 phosphorylation and localization. These approaches aim to restore blood-brain barrier integrity or modulate paracellular permeability depending on therapeutic context.

Drugs targeting OCLN would stabilize or enhance tight junction protein interactions, reinforcing the structural integrity of the blood-brain barrier and reducing pathological barrier permeability. Therapeutic approaches would involve either direct protein stabilization or indirect modulation of occludin phosphorylation and trafficking to maintain barrier function.

Direct PLIN2 inhibitors would reduce lipid droplet formation and stability, promoting lipid mobilization and reducing pathological lipid accumulation. Indirect approaches target upstream regulators of PLIN2 expression or modulate associated lipases to alter lipid storage dynamics in metabolic and neurodegenerative disease states.

Targeting protein-heparan sulfate interactions or enzymatic modification

Protein cleavage by botulinum toxin or small molecule modulators of SNARE complex formation

Drugs targeting GAP43 would enhance axonal growth cone formation and synaptic plasticity by promoting phosphorylation or membrane translocation of GAP43, thereby facilitating neurite outgrowth and synapse formation. Alternatively, agents could upregulate GAP43 expression to restore neuronal connectivity and compensate for age-related decline in neurodegenerative conditions.

Drug candidates would modulate FLOT1-mediated lipid raft organization and signaling platform assembly, thereby disrupting pathological protein trafficking and reducing amyloid-beta or tau-related pathology in neurodegenerative diseases. FLOT1 inhibitors would interfere with membrane scaffold formation necessary for aberrant signaling in neuroinflammatory and proteinopathic cascades.

No established drugging mechanism for structural membrane protein

Tight junction protein modulation - no established druggable mechanisms

Tight junction protein modulation - no established druggable mechanisms

Biomarker readout — GFAP levels reflect astrocyte reactivity; modulating upstream pathways (e.g., NF-κB, JAK-STAT) reduces GFAP expression

Drugs targeting MAP6 would stabilize microtubules through direct binding or modulation of MAP6's stabilizing activity, thereby promoting neuronal cytoskeletal integrity and synaptic function. This stabilization could enhance axonal transport, prevent neuronal degeneration, and support cognitive and synaptic plasticity in neurodegenerative conditions.

Tau aggregation inhibitors, anti-tau antibodies, tau phosphorylation modulators