Table 1 Targeting membrane receptors and proteins
Target | Function | Mechanism | In vivo evidence | In vitro evidence | Intervention | Therapies | |
|---|---|---|---|---|---|---|---|
LRP1 | Transmembrane receptor that regulates endocytosis of certain ligands | Uptakes and internalize α-syn and mediates spread | Yes | Yes | Inhibition and blocking of α-syn uptake | Limited research | |
LAG3 | Transmembrane protein that regulates immune cell homeostasis | Binding and internalizaion of α-syn PFFs | Yes | Yes | Blocking of α-syn binding | Anti-LAG3 antibodies | |
APLP1 | Bind proteins on surface of cells | APLP1 and LAG3 co-localize to form complex that binds and internalize α-syn | Yes | Yes | Blocking of α-syn binding | Limited research | [23] |
TLR4 | Membrane-bound receptor, induces innate immune response | Activation induces autophagy and α-syn clearance but also leads to prolonged inflammation | Yes | Yes | Activation promotes α-syn clearance and blocking reduces neuroinflammation | Limited research | |
α3-NKA | Membrane-bound protein that maintains electrochemical gradients | α-Syn co-clustering impairs maintenance functions | Prevent clustering and interactions with α-syn | Anti-NKA antibodies | Prevent clustering and interactions with α-syn | Anti-NKA antibodies | |
Integrin CD11b | Transmembrane receptor that facilitates cell-matrix adhesion | Binding to α-syn activates NADPH oxidase | Yes | Yes | Blocking α-syn binding attenuates α-syn-induced NOX2 activation | Limited research | |
FcγRIIB | Cell surface receptor that mediates immune responses | α-Syn binding inhibits microglial phagocytos and induces α-syn internalization and spread | Yes | Limited research | Blocking of α-syn binding | Limited research | |
HSPG | Cell surface receptors for proteases and protease inhibitors | Binding and uptake of α-syn PFFs seeds intracellular accumulation | Yes | Yes | Blocking of α-syn binding | Limited research | |
PrPc | Cell surface glycoprotein and a toxicity-transducing receptor | α-Syn binding triggers phosphorylation and alters calcium homeostasis | Yes | Yes | Blocking of α-syn binding | Limited research | |
GPNMB | Transmembrane glycoprotein involved with innate immune response | Co-localize and internalize α-syn fibrils | Yes | Yes | Blocking of α-syn binding | Limited research |