Utilizing Proteomic Approaches to Uncover the Neuroprotective Effects of ACE Inhibitors: Implications for Alzheimer’s Disease Treatment

Author:

Yang Ming-Hui12ORCID,Ho Tzu-Chuan3,Chang Chin-Chuan45,Su Yuh-Shan3,Yuan Cheng-Hui6,Chuang Kuo-Pin5789ORCID,Tyan Yu-Chang348101112ORCID

Affiliation:

1. Division of General & Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

2. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

3. Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan

4. Department of Nuclear Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

5. School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

6. Mass Spectrometry Laboratory, Department of Chemistry, National University of Singapore, Singapore 119077, Singapore

7. International Degree Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 912, Taiwan

8. Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan

9. Companion Animal Research Center, National Pingtung University of Science and Technology, Pingtung 912, Taiwan

10. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

11. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

12. Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Abstract

Two types of angiotensin-converting enzyme (ACE) inhibitors, lisinopril and benazepril HCl, were tested in neuroblastoma cells and found to upregulate low-density lipoprotein-receptor-related protein 1B (LRP1B) and 14-3-3 protein zeta/delta. Additionally, benazepril HCl was found to increase the expression of calreticulin. The upregulation of these proteins by ACE inhibitors may contribute to the amelioration of cognitive deficits in Alzheimer’s disease/dementia, as well as the clinically observed deceleration of functional decline in Alzheimer’s patients. This discovery suggests that the supplementation of ACE inhibitors may promote neuronal cell survival independently of their antihypertensive effect. Overall, these findings indicate that ACE inhibitors may be a promising avenue for developing effective treatments for Alzheimer’s disease.

Funder

Ministry of Science and Technology

Kaohsiung Medical University

NPUST-KMU JOINT RESEARCH PROJECT

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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