Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease

Abstract

Abstract:The adipocyte-secreted protein adiponectin (APN) has several protective functions in the peripheral tissues including insulin sensitizing, anti-inflammatory and anti-oxidative effects that may benefit neurodegenerative diseases such as Alzheimer's disease (AD). In addition, dysregulation of cerebral insulin sensitivities and signaling activities have been implicated in AD. Emerging insights into the mechanistic roles of adiponectin and AD highlight the potential therapeutic effects for AD through insulin signaling.

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

“…Insulin signaling in the brain reportedly regulates key processes, including neuronal growth, synaptic plasticity, and energy homeostasis [70], and the disruption of insulin signaling is recognized as an important risk factor for AD pathogenesis [50,71]. Noticeably, APN has been reported to have insulin-sensitizing and anti-inflammatory actions [72] by activating multiple signaling molecules.…”

“…Taken together, these findings indicated that HFDinduced oxidative stress mediates neuronal insulin resistance by impairing adipoR1/p-AMPK signaling both in vivo and in vitro. Previous studies have reported that, under physiological conditions, adiponectin (APN), through phosphorylation of adiponectin receptor 1 (AdipoR1), activates AMPK, and regulates insulin signaling in the brain [2,50]. However, HFD-induced obesity results in peripheral metabolic changes and significant reductions in AMPK levels in the brain [12,51].…”

Cord and Early Childhood Plasma Adiponectin Levels and Autism Risk: A Prospective Birth Cohort Study

“…Adiponectin enters the brain from circulation and directly targets neurons (Ng and Chan 2017; Thundyil et al 2012; D. Zhang et al 2016; Zhang et al 2017; Song et al 2015).…”

“…Given this broad distribution of adiponectin receptors in different brain regions, adiponectin’s role may be broader than the regulation of metabolic homeostasis and could plan an important role in the ‘adipocyte-brain cross-talk’ (Thundyil et al 2012). Adiponectin is involved in neurogenesis, dendritic spine remodeling, hippocampal neural stem cell proliferation and dentate gyrus neuronal excitability (Zhang et al 2017; Ng and Chan 2017; Song et al 2015; D. Zhang et al 2016).…”

“…For example, diminished adiponectin levels are associated with clinically significant affective episodes and subjects with major depressive symptoms are known to have lower adiponectin levels (Machado-Vieira et al 2017). Adiponectin knockout mice have exhibited depressive-like behavior (Ng and Chan 2017). Further, hypoadiponectinemia is thought to increase sympathetic nervous system activity – which is observed in depression (Lehto et al 2010).…”