Metabolic Syndrome, Brain Insulin Resistance, and Alzheimer's Disease

Thioredoxin Interacting Protein (TXNIP) and Inflammasome as Core Amplifiers

Sanaz Nasoohi, Kehkashan Parveen, Tauheed Ishrat

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)857-885
Number of pages29
JournalJournal of Alzheimer's Disease
Volume66
Issue number3
DOIs
StatePublished - Jan 1 2018

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Metabolic Brain Diseases
Inflammasomes
Thioredoxins
Insulin Resistance
Alzheimer Disease
Proteins
Oxidative Stress
Poisons
Type 2 Diabetes Mellitus
Dementia
Up-Regulation
Stroke
Insulin
Pathology
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Metabolic Syndrome, Brain Insulin Resistance, and Alzheimer's Disease : Thioredoxin Interacting Protein (TXNIP) and Inflammasome as Core Amplifiers. / Nasoohi, Sanaz; Parveen, Kehkashan; Ishrat, Tauheed.

In: Journal of Alzheimer's Disease, Vol. 66, No. 3, 01.01.2018, p. 857-885.

Research output: Contribution to journalReview article

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