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Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition
Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders. The etiology and pathology of AD are complicated, variable, and yet to be completely discovered. However, the involvement of inflammasomes, particularly the NLRP3 inflammasome, has been emphasized recently. NLRP3 is a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403980/ https://www.ncbi.nlm.nih.gov/pubmed/36006570 http://dx.doi.org/10.1007/s10753-022-01730-0 |
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author | Sharma, Barkha Satija, Garvit Madan, Anish Garg, Mansi Alam, M. Mumtaz Shaquiquzzaman, M. Khanna, Suruchi Tiwari, Prachi Parvez, Suhel Iqubal, Ashif Haque, Syed Ehtaishamul Khan, Mohammad Ahmed |
author_facet | Sharma, Barkha Satija, Garvit Madan, Anish Garg, Mansi Alam, M. Mumtaz Shaquiquzzaman, M. Khanna, Suruchi Tiwari, Prachi Parvez, Suhel Iqubal, Ashif Haque, Syed Ehtaishamul Khan, Mohammad Ahmed |
author_sort | Sharma, Barkha |
collection | PubMed |
description | Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders. The etiology and pathology of AD are complicated, variable, and yet to be completely discovered. However, the involvement of inflammasomes, particularly the NLRP3 inflammasome, has been emphasized recently. NLRP3 is a critical pattern recognition receptor involved in the expression of immune responses and has been found to play a significant role in the development of various immunological and neurological disorders such as multiple sclerosis, ulcerative colitis, gout, diabetes, and AD. It is a multimeric protein which releases various cytokines and causes caspase-1 activation through the process known as pyroptosis. Increased levels of cytokines (IL-1β and IL-18), caspase-1 activation, and neuropathogenic stimulus lead to the formation of proinflammatory microglial M1. Progressive researches have also shown that besides loss of neurons, the pathophysiology of AD primarily includes amyloid beta (Aβ) accumulation, generation of oxidative stress, and microglial damage leading to activation of NLRP3 inflammasome that eventually leads to neuroinflammation and dementia. It has been suggested in the literature that suppressing the activity of the NLRP3 inflammasome has substantial potential to prevent, manage, and treat Alzheimer’s disease. The present review discusses the functional composition, various models, signaling molecules, pathways, and evidence of NLRP3 activation in AD. The manuscript also discusses the synthetic drugs, their clinical status, and projected natural products as a potential therapeutic approach to manage and treat NLRP3 mediated AD. |
format | Online Article Text |
id | pubmed-9403980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-94039802022-08-25 Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition Sharma, Barkha Satija, Garvit Madan, Anish Garg, Mansi Alam, M. Mumtaz Shaquiquzzaman, M. Khanna, Suruchi Tiwari, Prachi Parvez, Suhel Iqubal, Ashif Haque, Syed Ehtaishamul Khan, Mohammad Ahmed Inflammation Review Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders. The etiology and pathology of AD are complicated, variable, and yet to be completely discovered. However, the involvement of inflammasomes, particularly the NLRP3 inflammasome, has been emphasized recently. NLRP3 is a critical pattern recognition receptor involved in the expression of immune responses and has been found to play a significant role in the development of various immunological and neurological disorders such as multiple sclerosis, ulcerative colitis, gout, diabetes, and AD. It is a multimeric protein which releases various cytokines and causes caspase-1 activation through the process known as pyroptosis. Increased levels of cytokines (IL-1β and IL-18), caspase-1 activation, and neuropathogenic stimulus lead to the formation of proinflammatory microglial M1. Progressive researches have also shown that besides loss of neurons, the pathophysiology of AD primarily includes amyloid beta (Aβ) accumulation, generation of oxidative stress, and microglial damage leading to activation of NLRP3 inflammasome that eventually leads to neuroinflammation and dementia. It has been suggested in the literature that suppressing the activity of the NLRP3 inflammasome has substantial potential to prevent, manage, and treat Alzheimer’s disease. The present review discusses the functional composition, various models, signaling molecules, pathways, and evidence of NLRP3 activation in AD. The manuscript also discusses the synthetic drugs, their clinical status, and projected natural products as a potential therapeutic approach to manage and treat NLRP3 mediated AD. Springer US 2022-08-25 2023 /pmc/articles/PMC9403980/ /pubmed/36006570 http://dx.doi.org/10.1007/s10753-022-01730-0 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Review Sharma, Barkha Satija, Garvit Madan, Anish Garg, Mansi Alam, M. Mumtaz Shaquiquzzaman, M. Khanna, Suruchi Tiwari, Prachi Parvez, Suhel Iqubal, Ashif Haque, Syed Ehtaishamul Khan, Mohammad Ahmed Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition |
title | Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition |
title_full | Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition |
title_fullStr | Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition |
title_full_unstemmed | Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition |
title_short | Role of NLRP3 Inflammasome and Its Inhibitors as Emerging Therapeutic Drug Candidate for Alzheimer’s Disease: a Review of Mechanism of Activation, Regulation, and Inhibition |
title_sort | role of nlrp3 inflammasome and its inhibitors as emerging therapeutic drug candidate for alzheimer’s disease: a review of mechanism of activation, regulation, and inhibition |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403980/ https://www.ncbi.nlm.nih.gov/pubmed/36006570 http://dx.doi.org/10.1007/s10753-022-01730-0 |
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