Correspondence:
[*]
Correspondence to: Tauheed Ishrat, PhD, University of Tennessee Health Science Center, College of Medicine, Department of Anatomy and Neurobiology, 855 Monroe Avenue, Wittenborg Bldg, Room-231, Memphis, TN 38163, USA. Tel.: +1 901 448 2178; Fax: +1 901 448 7193; E-mail: [email protected].
Abstract: Empirical evidence indicates a strong association between insulin resistance and pathological alterations related to Alzheimer’s disease (AD) in different cerebral regions. While cerebral insulin resistance is not essentially parallel with systemic metabolic derangements, type 2 diabetes mellitus (T2DM) has been established as a risk factor for AD. The circulating “toxic metabolites” emerging in metabolic syndrome may engage several biochemical pathways to promote oxidative stress and neuroinflammation leading to impair insulin function in the brain or “type 3 diabetes”. Thioredoxin-interacting protein (TXNIP) as an intracellular amplifier of oxidative stress and inflammasome activation may presumably mediate central insulin resistance. Emerging data including those from our recent studies has demonstrated a sharp TXNIP upregulation in stroke, aging and AD and well underlining the significance of this hypothesis. With the main interest to illustrate TXNIP place in type 3 diabetes, the present review primarily briefs the potential mechanisms contributing to cerebral insulin resistance in a metabolically deranged environment. Then with a particular focus on plausible TXNIP functions to drive and associate with AD pathology, we present the most recent evidence supporting TXNIP as a promising therapeutic target in AD as an age-associated dementia.
Keywords: Alzheimer’s disease, brain insulin resistance, inflammasomes, metabolic
syndrome, oxidative stress, thioredoxin-interacting protein (TXNIP), type 3 diabetes
