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Amyloid beta peptide-degrading microbial enzymes and its implication in drug design

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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.

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Acknowledgements

KDS is thankful to University Grants Commission, New Delhi for providing financial support under UGC SAP DRS Phase-II programme sanctioned to Department of Biochemistry, Shivaji University, Kolhapur. Authors are thankful to Department of Science and Technology, New Delhi for providing fellowship as research assistance under DST-PURSE scheme.

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  1. Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur, Maharashtra, 416004, India

    Kailas D. Sonawane

  2. Department of Microbiology, Shivaji University, Kolhapur, Maharashtra, 416004, India

    Maruti J. Dhanavade & Kailas D. Sonawane

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Dhanavade, M.J., Sonawane, K.D. Amyloid beta peptide-degrading microbial enzymes and its implication in drug design. 3 Biotech 10, 247 (2020). https://doi.org/10.1007/s13205-020-02240-2

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