Protective Effect of Tat PTD-Hsp27 Fusion Protein on Tau Hyperphosphorylation Induced by Okadaic Acid in the Human Neuroblastoma Cell Line SH-SY5Y.

Abstract

Alzheimer's disease (AD) is an age-related disorder that causes a loss of brain function. Hyperphosphorylation of tau and the subsequent formation of intracellular neurofibrillary tangles (NFTs) are implicated in the pathogenesis of AD. Hyperphosphorylated tau accumulates into insoluble paired helical filaments that aggregate into NFTs; therefore, regulation of tau phosphorylation represents an important treatment approach for AD. Heat shock protein 27 (Hsp27) plays a specific role in human neurodegenerative diseases; however, few studies have examined its therapeutic effect. In this study, we induced tau hyperphosphorylation using okadaic acid, which is a protein phosphatase inhibitor, and generated a fusion protein of Hsp27 and the protein transduction domain of the HIV Tat protein (Tat-Hsp27) to enhance the delivery of Hsp27. We treated Tat-Hsp27 to SH-SY5Y neuroblastoma cells for 2 h; the transduction level was proportional to the Tat-hsp27 concentration. Additionally, Tat-Hsp27 reduced the level of hyperphosphorylated tau and protected cells from apoptotic cell death caused by abnormal tau aggregates. These results reveal that Hsp27 represents a valuable protein therapeutic for AD.

• Authors: Sunghyun Choi, Jae Hoon Oh, Hyeseon Kim, So Hee Nam, Jeehae Shin, Jong-Sang Park
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 35 Issue 7 Pg. 1049-59 (Oct 2015) ISSN: 1573-6830 [Electronic] United States
• PMID: 25990227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Neuroprotective Agents
• Recombinant Fusion Proteins
• tat Gene Products, Human Immunodeficiency Virus
• tau Proteins
• Okadaic Acid

Topics

• Cell Line, Tumor
• Dose-Response Relationship, Drug
• HSP27 Heat-Shock Proteins (administration & dosage)
• Heat-Shock Proteins
• Humans
• Molecular Chaperones
• Neuroblastoma (metabolism)
• Neuroprotective Agents (administration & dosage)
• Okadaic Acid (toxicity)
• Phosphorylation (drug effects, physiology)
• Recombinant Fusion Proteins (administration & dosage)
• tat Gene Products, Human Immunodeficiency Virus (administration & dosage)
• tau Proteins (metabolism)