[Aβ Receptor PirB and its regulation by LOTUS]

Over the years, research has accumulated a vast amount of knowledge about the pathogenesis of dementia, including Alzheimer's disease (AD). However, fundamental treatments for AD have not yet been established. In this article, we discuss an Aβ receptor, paired immunoglobulin like receptor B (PirB) and its endogenous regulator lateral olfactory tract usher substance (LOTUS), which are completely different novel drug target from existing drugs, and the possibility of endogenous inhibitors of PirB. PirB expressed in neurons is a negative regulator of neuronal plasticity, as loss or inhibition of PirB increases neuronal plasticity, leading to increased spine density and improved cognitive function. Furthermore, PirB is known to function as a receptor for Aβ, leading to reduced neuronal plasticity and cell death. These findingss suggest that PirB can be positioned as a novel drug target for the treatment of AD. The neuronal circuit-forming factor LOTUS, which binds to PirB and functions as an endogenous antagonist, has been shown to inhibit the neurotoxic effects of Aβ mediated by PirB. Namely, LOTUS is an endogenous molecule that inhibits Aβ receptor function of PirB and may have medicinal effects against Aβ pathology.