The 4-(Phenylsulfanyl) butan-2-one Improves Impaired Fear Memory Retrieval and Reduces Excessive Inflammatory Response in Triple Transgenic Alzheimer's Disease Mice
Authors: Peeraporn Varinthra
Shun-Ping Huang
Chatchakorn Eurtivong
Kiruthika Ganesan
Pavithra Suresh
Zhi-Hong Wen
Supin Chompoopong
Ingrid Y Liu
Journal: Frontiers in aging neuroscience (2021)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: 3xTg-AD; 4-(phenylsulfanyl) butan-2-one; Alzheimer's disease; CA3; fear conditioning
Affiliations: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan., Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan., Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand., Program in Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand., Center of Excellence on Environmental Health and Toxicology (EHT), Commission on Higher Education (CHE), Ministry of Education, Bangkok, Thailand., Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.

Abstract:  Alzheimer's disease (AD) is a neurodegenerative disease characterized by an excessive inflammatory response and impaired memory retrieval, including spatial memory, recognition memory, and emotional memory. Acquisition and retrieval of fear memory help one avoid dangers and natural threats. Thus, it is crucial for survival. AD patients with impaired retrieval of fear memory are vulnerable to dangerous conditions. Excessive expression of inflammatory markers is known to impede synaptic transmission and reduce the efficiency of memory retrieval. In wild-type mice, reducing inflammation response can improve fear memory retrieval; however, this effect of this approach is not yet investigated in 3xTg-AD model mice. To date, no satisfactory drug or treatment can attenuate the symptoms of AD despite numerous efforts. In the past few years, the direction of therapeutic drug development for AD has been shifted to natural compounds with anti-inflammatory effect. In the present study, we demonstrate that the compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) is effective in enhancing fear memory retrieval of wild-type and 3xTg-AD mice by reducing the expression of TNF-α, COX-2, and iNOS. We also found that 4-PSB-2 helps increase dendritic spine density, postsynaptic density protein-95 (PSD-95) expression, and long-term potentiation (LTP) in the hippocampus of 3xTg-AD mice. Our study indicates that 4-PSB-2 may be developed as a promising therapeutic compound for treating fear memory impairment of AD patients. 

Retracted: No

PubPeer comments:
 In right column, page 2, this article pointed out that the compound 4-(Phenylsulfanyl) butan-2-one ( 4-PSB-2) was initially extracted from the soft coral Cladiella australis, however, 4-PSB-2 has never been reported to be isolated from the soft coral Cladiella australis via a thorough literature search. In left column, page 3, it was claimed that 4-PSB-2 was provided by the Research Center of National Research Program for Biopharmaceuticals, Taiwan. In right column, page 5, it was further mentioned that the compound 4-PSB-2 was initially extracted from a soft coral Cladiella australis, then modified and synthesized by the Development Center for Biotechnology (Taiwan), the National Research Program for Biopharmaceuticals support (CS-1-G-103-002). If 4-PSB-2 was modified, which compound is the product of this modification, and why this modification has to be done. Finally, it is puzzled to see the statement in right column, page 14, that Z-HW provided the compound and helped interpret results. All authors read and approved the final version of this manuscript. , 
 In the right column of page 13 of this article, the following statement was observed. The 4-PSB-2 has a similar chemical structure as BAY 11-7082 reported in a previous study (Lee et al., 2012), which can also suppress the expression of inflammatory proteins, including Iu03baB, NF-u03baB, and Akt. The structure of BAY 11- 7082 varies slightly from that of 4-PSB-2, as it contains a reactive Michael acceptor and a cyanide group in place of a ketone group. The structural similarities of the compounds probably underlie their similar functions in suppressing the inflammatory response. But the phenyl, sulfanyl, saturated ethylene (-CH2CH2-), and carbonyl groups of 4-PSB-2 are all quite different to the 4-methylphenyl, sulfone, unasturated acetylene (-cH=CH-), and cyanide groups of BAY 11-7082 , respectively. How can the authors tell that 4-PSB-2 has a similar chemical structure as BAY 11-7082 and the structural similarities of both compounds probably underlie their similar functions in suppressing the inflammatory response? ,