Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer’s Disease (sAD)-Like Pathology

Pradip K. Kamat, Anuradha Kalani, Shivika Rai, Santosh Kumar Tota, Ashok Kumar, Abdullah S. Ahmad

Research output: Contribution to journalReview article

37 Scopus citations

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer’s disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology.

Original languageEnglish (US)
Pages (from-to)4548-4562
Number of pages15
JournalMolecular Neurobiology
Volume53
Issue number7
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Insulin
  • Kinase
  • Neuroinflammation
  • Streptozotocin

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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