Roles of Neuropeptide Y in Neurodegenerative and Neuroimmune Diseases

Abstract

Neuropeptide Y (NPY) is a neurotransmitter or neuromodulator that mainly exists in the nervous system. It plays a neuroprotective role in organisms and widely participates in the regulation of various physiological processes in vivo. Studies in both humans and animal models have been revealed that NPY levels are altered in some neurodegenerative and neuroimmune disorders. NPY plays various roles in these diseases, such as exerting a neuroprotective effect, increasing trophic support, decreasing excitotoxicity, regulating calcium homeostasis, and attenuating neuroinflammation. In this review, we will focus on the roles of NPY in the pathological mechanisms of neurodegenerative and neuroimmune diseases, highlighting NPY as a potential therapeutic target in these diseases.

Keywords: Alzheimer’s disease; Guillain-Barré syndrome; Parkinson’s disease; neurodegenerative diseases; neuroimmune disorders; neuropeptide Y.

FIGURE 1

Related mechanism of NPY in neurodegenerative diseases. The neuroprotective and anti-neuroinflammatory roles of NPY in neurodegenerative diseases include modulating neurogenesis, increasing trophic support, exerting neuroprotective effects, affecting some clinical manifestations, attenuating neuroinflammation, and stimulating autophagy.

FIGURE 2

Possible action of NPY in GBS/EAN. T cells are activated by unknown antigens on antigen-presenting cells (APCs) through a combination of major histocompatibility complex (MHC), T cell receptor (TCR), and co-stimulatory signals in the systemic immune system. These activated neurogenic T cells differentiate into pro-inflammatory T helper cells (Th1, Th2, and Th17) and regulatory cell (Treg). Th1 secretes pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ and interleukin (IL)-12 to activate macrophages (MΦ). MΦ have been primarily divided into two distinct subsets: pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2). M1 macrophages promote breakdown of the blood-nerve barrier (BNB) by releasing nitric oxide (NO), matrix metalloproteases (MMPs), and TNF-α. M2 macrophages promote remyelination and tissue repair by secreting anti-inflammatory cytokines such as IL-10 and tumor growth factor (TGF-β) and promoting T-cell apoptosis. NPY shifts the Th1/Th2 balance toward the Th2 phenotype, activating secretion of IL-4 and TGF-β, and inhibiting secretion of IFN-γ and TNF-α.