Table 3 Key Receptors Involved in Microglial Activation.

From: The multifaceted roles of apolipoprotein E4 in Alzheimer’s disease pathology and potential therapeutic strategies

Receptors

Receptor type

Biological function

Implications in AD

Ref.

TREM2

Member of the immunoglobulin-like receptor family

Binds to ApoE4, Aβ, and HMGB1, promoting microglial activation and immune response

TREM2 deletion reduces microglial survival, impairs phagocytosis, and inhibits Aβ clearance

[157]

CD33

Member of the SIGLEC family proteins

Binds to Aβ, suppressing microglial phagocytosis and immune responses

Overexpression of CD33 limits Aβ clearance and enhances inflammation

[158]

LRP1

Member of the LDL receptor family, a large transmembrane receptor

Binds to Aβ, lipoproteins, and other ligands, regulating microglial activation and promoting Aβ clearance

LRP1 dysfunction impairs Aβ clearance and promotes chronic inflammation

[159]

P2Y Receptors

Member of the G-protein coupled receptor family

Binds to ATP and other purines, activating microglial responses to danger signals and promoting migration

Overactivation promotes excessive microglial inflammation

[160]

TLR4

Member of the Toll-like receptor family

Binds to Aβ, PAMPs, and DAMPs, activating microglial inflammation and immune responses

TLR4 activation promotes microglial inflammation and neurodegeneration in AD

[161]

LilrB3

Member of the LILR family proteins

Binds to ApoE4, promoting microglial activation and a pro-inflammatory response

LilrB3 interacts with ApoE4, driving microglial inflammation and impairing phagocytosis

[162]

RAGE

Member of the AGE receptor family

Binds to Aβ, HMGB1, and other DAMPs, activating microglial inflammation and promoting immune responses

RAGE activation enhances microglial activation and intensifies the inflammatory response and oxidative stress in the brain

[163]

CD36

Member of the scavenger receptor family

Binds to Aβ, oxidized lipids, PAMPs, and DAMPs, enhancing microglial phagocytosis and inflammatory responses

CD36 activation can enhance Aβ clearance but also promotes neuroinflammation

[164]

SCARA-1

Member of the scavenger receptor family

Binds to Aβ and apoptotic cells, promoting microglial phagocytosis and immune responses

SCARA-1 deficiency reduces Aβ clearance

[165]

Fc Receptors

Member of the immunoglobulin receptor family

Binds to immunoglobulin complexes and Aβ, promoting microglial activation and phagocytosis

Fc receptor activation enhances Aβ clearance but can also increase inflammation

[166]

Complement Receptor

Member of the complement receptor family

Bind to complement-opsonized Aβ, enhancing microglial phagocytosis and immune activation

Complement receptor activation may aid Aβ clearance but also promote neuroinflammation

[167]

  1. CR Complement Receptor; DAMPs Damage-associated molecular patterns; FPR Formyl Peptide Receptor; HMGB1 High Mobility Group Box 1; LDL Low-density lipoprotein; LILR Leukocyte immunoglobulin-like receptor; LPS Lipopolysaccharides; MAC1 Macrophage-1 Antigen; PAMPs Pathogen-associated molecular patterns; SIGLEC Sialic acid-binding immunoglobulin-like lectin; SR Scavenger Receptor; TLR Toll-like Receptor; TREM-2 Triggering Receptor Expressed on Myeloid Cells-2.
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