Amyloid beta peptide-degrading microbial enzymes and its implication in drug design
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REVIEW ARTICLE
Amyloid beta peptide‑degrading microbial enzymes and its implication in drug design Maruti J. Dhanavade2 · Kailas D. Sonawane1,2 Received: 30 November 2017 / Accepted: 30 April 2020 © King Abdulaziz City for Science and Technology 2020
Abstract Alzheimer’s disease (AD) is a chronic and progressive neurological brain disorder. AD pathophysiology is mainly represented by formation of neuritic plaques and neurofibrillary tangles (NFTs). Neuritic plaques are made up of amyloid beta (Aβ) peptides, which play a central role in AD pathogenesis. In AD brain, Aβ peptide accumulates due to overproduction, insufficient clearance and defective proteolytic degradation. The degradation and cleavage mechanism of Aβ peptides by several human enzymes have been discussed previously. In the mean time, numerous experimental and bioinformatics reports indicated the significance of microbial enzymes having potential to degrade Aβ peptides. Thus, there is a need to shift the focus toward the substrate specificity and structure–function relationship of Aβ peptide-degrading microbial enzymes. Hence, in this review, we discussed in vitro and in silico studies of microbial enzymes viz. cysteine protease and zinc metallopeptidases having ability to degrade Aβ peptides. In silico study showed that cysteine protease can cleave Aβ peptide between Lys16–Cys17; similarly, several other enzymes also showed capability to degrade Aβ peptide at different sites. Thus, this review paves the way to explore the role of microbial enzymes in Aβ peptide degradation and to design new lead compounds for AD treatment. Keywords Alzheimer’s disease · Amyloid β-peptide · Aβ-degrading enzymes · Molecular modeling
Introduction Alzheimer’s disease (AD) is a neurological disorder of brain. It has been reported in the year 2000 that nearly 25 million people were affected worldwide by AD and this number would reach up to 63 and 114 millions by 2030 and 2050, respectively (Loncarevic et al. 2005). Because of this, AD is a serious problem in terms of medical and financial views to the society. There are different hypotheses in AD, including cholinergic, amyloid cascade, tau, oxidative imbalance and mild cognitive impairment (Schneider et al. 2011; Love et al. 2009; Ballard et al. 2011; Hardy and Selkoe 2002; Glenner and Wong 1984). The hypotheses, concepts and theories regarding AD have been discussed in earlier review (Barage and Sonawane 2015). In the cholinergic hypothesis, shortage of neurotransmitters like acetylcholine and butyrylcholine * Kailas D. Sonawane [email protected] 1
Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur, Maharashtra 416004, India
Department of Microbiology, Shivaji University, Kolhapur, Maharashtra 416004, India
2
have been identified (Schneider et al. 2011). Therefore, inhibition of enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE) which are responsible to break down acetylcholine and butyrylcholine has been considered as a standard approa
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