The Binding Receptors of Aβ: an Alternative Therapeutic Target for Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, which causes the deterioration of memory and other cognitive abilities of the elderly. Previous lines of research have shown that Aβ is an essential factor in AD pathology and the soluble oligomeric species of Aβ peptide is presumed to be the drivers of synaptic impairment in AD. However, the exact mechanisms underlying Aβ-induced synapse dysfunction are still not fully understood. Recently, increasing evidence suggests that some potential receptors which bind specifically with Aβ may play important roles in inducing the toxicity of the neurons in AD pathology. These receptors include the cellular prion protein (PrPc), the α7 nicotinic acetylcholine receptor (α7nAChR), the p75 neurotrophin receptor (p75(NTR)), the beta-adrenergic receptors (β-ARs), the Eph receptors, the paired immunoglobulin-like receptor B (PirB), the PirB's human ortholog receptor (LilrB2), and the Fcγ receptor II-b (FcγRIIb). This review summarizes the characters of these prominent receptors and how the bindings of them with Aβ inhibit the LTP, decrease the number of dendritic spine, damage the neurons, and so on in AD pathogenesis. Blocking or rescuing these receptors may have significant importance for AD treatments.

Tau phosphorylation induced by severe closed head traumatic brain injury is linked to the cellular prion protein

“…In addition, the Aβo-PrP C interaction has been linked to memory impairments in multiple AD mouse models [20]. The blocking of binding between Aβo and PrP C is currently being tested as a therapeutic approach to prevent or treat AD pathology [9, 20, 60]. …”

Plant alkaloids as drug leads for Alzheimer's disease

“…A C C E P T E D ACCEPTED MANUSCRIPT 4 on deposited Aβ as the major cause of pathogenesis, mounting evidence suggests that the soluble oligomeric species of Aβ actually mediates the synaptic dysfunctions in AD (Paula-Lima et al, 2013;Fu et al, 2014;Tu et al, 2014;Xia et al, 2014). Oligomeric Aβ can bind to its potential receptors, which are expressed on astrocytes, microglia, and neurons, to induce synaptic toxicity; these receptors include N-methyl-D-aspartate receptor (NMDAR), cellular prion protein, α7 nicotinic acetylcholine receptor (nAChR), p75 neurotrophin receptor, β-adrenergic receptors, erythropoietin-producing hepatocellular (Eph) receptors, paired immunoglobulin-like receptor B, PirB's human ortholog receptor, and Fcγ receptor II-b (Tu et al, 2014;Xia et al, 2014).…”

“…Oligomeric Aβ can bind to its potential receptors, which are expressed on astrocytes, microglia, and neurons, to induce synaptic toxicity; these receptors include N-methyl-D-aspartate receptor (NMDAR), cellular prion protein, α7 nicotinic acetylcholine receptor (nAChR), p75 neurotrophin receptor, β-adrenergic receptors, erythropoietin-producing hepatocellular (Eph) receptors, paired immunoglobulin-like receptor B, PirB's human ortholog receptor, and Fcγ receptor II-b (Tu et al, 2014;Xia et al, 2014). Thus, extensive efforts have targeted the Aβ cascade through inhibition and modulation of secretase activities, with the aim of counteracting the formation of Aβ aggregates or removing various Aβ forms.…”

Role of amyloid β protein receptors in mediating synaptic plasticity

“…Aβ oligomers exert effects on synaptic plasticity and memory by binding to associated receptors and thereby activating downstream signaling (30,31 , which invades the central nervous system of humans, and has a long incubation period and poor prognosis. Although AD and CJD are different types of diseases, they belong to misfolded protein diseases, which are characterized by abnormal protein folding that translates the α-helix into a beta sheet.…”