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Planta Med 2019; 85(17): 1316-1325
DOI: 10.1055/a-1019-9819
Biological and Pharmacological Activity
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Georg Thieme Verlag KG Stuttgart · New York

Natural Compounds with Anti-BACE1 Activity as Promising Therapeutic Drugs for Treating Alzheimerʼs Disease

Mehjabeen Naushad‡
1   Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, India
,
Siva Sundara Kumar Durairajan‡
1   Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, India
,
Amal Kanti Bera
2   Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
,
Sanjib Senapati
2   Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India
,
Min Li
3   Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinsonʼs Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
› Author Affiliations
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Publication History

received 08 April 2019
revised 24 September 2019

accepted 26 September 2019

Publication Date:
16 October 2019 (online)

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Abstract

Alzheimerʼs disease is a neurodegenerative disease that leads to irreversible neuronal damage. Senile plaques, composed of amyloid beta peptide, is the principal abnormal characteristic of the disease. Among the factors involved, the secretase enzymes, namely, α secretase, beta-site amyloid precursor protein-cleaving enzyme, β secretase, and γ secretase, hold consequential importance. Beta-site amyloid precursor protein-cleaving enzyme 1 is considered to be the rate-limiting factor in the production of amyloid beta peptide. Research supporting the concept of inhibition of beta-site amyloid precursor protein-cleaving enzyme activity as one of the effective therapeutic targets in the mitigation of Alzheimerʼs disease is well accepted. The identification of natural compounds, such as β-amyloid precursor protein-selective beta-site amyloid precursor protein-cleaving enzyme inhibitors, and the idea of compartmentalisation of the beta-site amyloid precursor protein-cleaving enzyme 1 action have caused a dire need to closely examine the natural compounds and their effectiveness in the disease mitigation. Many natural compounds have been reported to effectively modulate beta-site amyloid precursor protein-cleaving enzyme 1. At lower doses, compounds like 2,2′,4′-trihydroxychalcone acid, quercetin, and myricetin have been shown to effectively reduce beta-site amyloid precursor protein-cleaving enzyme 1 activity. The currently used five drugs that are marketed and used for the management of Alzheimerʼs disease have an increased risk of toxicity and restricted therapeutic efficiency, hence, the search for new anti-Alzheimerʼs disease drugs is of primary concern. A variety of natural compounds having pure pharmacological moieties showing multitargeting activity and others exhibiting specific beta-site amyloid precursor protein-cleaving enzyme 1 inhibition as discussed below have superior biosafety. Many of these compounds, which are isolated from medicinal herbs and marine flora, have been long used for the treatment of various ailments since ancient times in the Chinese and Ayurvedic medical systems. The aim of this article is to review the available data on the selected natural compounds, giving emphasis to the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 activity as a mode of Alzheimerʼs disease treatment.

Key words

Alzheimerʼs disease - BACE1 - BACE1 inhibitors - flavonoids - phenolics - alkaloids - terpenes