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.
Highlights
The central nervous system (CNS) is separated from the peripheral circulations by the blood-brain barrier (BBB), which stringently controls substance penetration in order to protect the brain from pathogenic micro-organisms and harmful toxins
There are several proposed mechanisms that link insulin to Alzheimer’s disease (AD): (1) high insulin level in diabetic patients leads to the competition of insulin degrading enzyme (IDE) with Aβ and thereby reduces the clearance of Aβ in the brain; (2) Aβ oligomers can bind to insulin receptors and block the insulin signaling pathways; (3) Aβ oligomers binding may downregulate insulin receptors via insulin receptor internalization; and (4) in obese or Type 2 Diabetes Mellitus (T2DM) subjects who are characterized by increased peripheral levels of tumor necrosis factor-α (TNFα), TNFα can cross the blood-brain barrier, which results in cerebral insulin resistance due to JNK activation
No cause-and-effect study had been conducted until we recently reported that chronic adiponectin deficiency elicited AD-like phenotypes, pathologies and cognitive impairments with cerebral insulin resistance in aged mice [86]
Summary
The central nervous system (CNS) is separated from the peripheral circulations by the blood-brain barrier (BBB), which stringently controls substance penetration in order to protect the brain from pathogenic micro-organisms and harmful toxins. The CNS receives and integrates information to coordinate the whole body’s activities. Peripheral tissues can produce chemokines and cytokines to regulate homeostasis and metabolism in the CNS. White adipose tissue is an endocrine tissue that secretes adipokines, which exert pleiotropic effects in different tissues. Several adipokine receptors including adiponectin, leptin, and resistin receptors are abundantly expressed in different brain regions. Dysregulation of adipokine production and/or levels is associated with neurological and neurodegenerative diseases that can notably be a result of obesity-related metabolic disorders. We will discuss the plausible mechanisms of adiponectin (APN) and its protective effects in Alzheimer’s disease
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