Tags

Type your tag names separated by a space and hit enter

Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications.
J Alzheimers Dis. 2015; 48(4):891-917.JA

Abstract

Alzheimer's disease (AD) is a neurodegenerative process primarily characterized by amyloid-β (Aβ) agglomeration, neuroinflammation, and cognitive dysfunction. The prominent cause for dementia is the deposition of Aβ plaques and tau-neurofibrillary tangles that hamper the neuronal organization and function. Aβ pathology further affects numerous signaling cascades that disturb the neuronal homeostasis. For instance, Aβ deposition is responsible for altered expression of insulin encoding genes that lead to insulin resistance, and thereby affecting insulin signaling pathway and glucose metabolism in the brain. As a result, the common pathology of insulin resistance between Type-2 diabetes mellitus and AD has led AD to be proposed as a form of diabetes and termed 'Type-3 diabetes'. Since accumulation of Aβ is the prominent cause of neuronal toxicity in AD, its clearance is the prime requisite for therapeutic prospects. This purpose is expertly fulfilled by the potential role of Aβ degrading enzymes such as insulin degrading enzyme (IDE) and Neprilysin (NEP). Therefore, their molecular study is important to uncover the proteolytic and regulatory mechanism of Aβ degradation. Herein, (i) In silico sequential and structural analysis of IDE and NEP has been performed to identify the molecular entities for proteolytic degradation of Aβ in the AD brain, (ii) to analyze their catalytic site to demonstrate the enzymatic action played by IDE and NEP, (iii) to identify their structural homologues that could behave as putative partners of IDE and NEP with similar catalytic action and (iv) to illustrate various IDE- and NEP-mediated therapeutic approaches and factors for clearing Aβ in AD.

Authors+Show Affiliations

Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India.Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India.Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India.Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India.Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India.Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India.Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Delhi, India. Department of Neurology, Tufts University School of Medicine, Boston, MA, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26444774

Citation

Jha, Niraj Kumar, et al. "Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications." Journal of Alzheimer's Disease : JAD, vol. 48, no. 4, 2015, pp. 891-917.
Jha NK, Jha SK, Kumar D, et al. Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications. J Alzheimers Dis. 2015;48(4):891-917.
Jha, N. K., Jha, S. K., Kumar, D., Kejriwal, N., Sharma, R., Ambasta, R. K., & Kumar, P. (2015). Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications. Journal of Alzheimer's Disease : JAD, 48(4), 891-917. https://doi.org/10.3233/JAD-150379
Jha NK, et al. Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications. J Alzheimers Dis. 2015;48(4):891-917. PubMed PMID: 26444774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications. AU - Jha,Niraj Kumar, AU - Jha,Saurabh Kumar, AU - Kumar,Dhiraj, AU - Kejriwal,Noopur, AU - Sharma,Renu, AU - Ambasta,Rashmi K, AU - Kumar,Pravir, PY - 2015/10/8/entrez PY - 2015/10/8/pubmed PY - 2016/8/4/medline KW - Alzheimer’s disease KW - Neprilysin KW - amyloid-β KW - insulin degrading enzyme KW - therapeutics SP - 891 EP - 917 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 48 IS - 4 N2 - Alzheimer's disease (AD) is a neurodegenerative process primarily characterized by amyloid-β (Aβ) agglomeration, neuroinflammation, and cognitive dysfunction. The prominent cause for dementia is the deposition of Aβ plaques and tau-neurofibrillary tangles that hamper the neuronal organization and function. Aβ pathology further affects numerous signaling cascades that disturb the neuronal homeostasis. For instance, Aβ deposition is responsible for altered expression of insulin encoding genes that lead to insulin resistance, and thereby affecting insulin signaling pathway and glucose metabolism in the brain. As a result, the common pathology of insulin resistance between Type-2 diabetes mellitus and AD has led AD to be proposed as a form of diabetes and termed 'Type-3 diabetes'. Since accumulation of Aβ is the prominent cause of neuronal toxicity in AD, its clearance is the prime requisite for therapeutic prospects. This purpose is expertly fulfilled by the potential role of Aβ degrading enzymes such as insulin degrading enzyme (IDE) and Neprilysin (NEP). Therefore, their molecular study is important to uncover the proteolytic and regulatory mechanism of Aβ degradation. Herein, (i) In silico sequential and structural analysis of IDE and NEP has been performed to identify the molecular entities for proteolytic degradation of Aβ in the AD brain, (ii) to analyze their catalytic site to demonstrate the enzymatic action played by IDE and NEP, (iii) to identify their structural homologues that could behave as putative partners of IDE and NEP with similar catalytic action and (iv) to illustrate various IDE- and NEP-mediated therapeutic approaches and factors for clearing Aβ in AD. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26444774/Impact_of_Insulin_Degrading_Enzyme_and_Neprilysin_in_Alzheimer's_Disease_Biology:_Characterization_of_Putative_Cognates_for_Therapeutic_Applications_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-150379 DB - PRIME DP - Unbound Medicine ER -