Inflammatory signaling pathways in Alzheimer's disease: Mechanistic insights and possible therapeutic interventions

Abdulmajeed G Almutary; M Yasmin Begum; Ashish Kumar Kyada; Saurabh Gupta; S Renuka Jyothi; Kamlesh Chaudhary; Swati Sharma; Aashna Sinha; Mosleh Mohammad Abomughaid; Mohd Imran; Sorabh Lakhanpal; Ahmad O Babalghith; Eman Adnan Abu-Seer; D Avinash; Hassan A Alzahrani; Abdulghani A Alhindi; Danish Iqbal; Sandeep Kumar; Niraj Kumar Jha; Saad Alghamdi

doi:10.1016/j.arr.2024.102548

Inflammatory signaling pathways in Alzheimer's disease: Mechanistic insights and possible therapeutic interventions

Ageing Res Rev. 2024 Oct 16:104:102548. doi: 10.1016/j.arr.2024.102548. Online ahead of print.

Authors

Abdulmajeed G Almutary¹, M Yasmin Begum², Ashish Kumar Kyada³, Saurabh Gupta⁴, S Renuka Jyothi⁵, Kamlesh Chaudhary⁶, Swati Sharma⁷, Aashna Sinha⁸, Mosleh Mohammad Abomughaid⁹, Mohd Imran¹⁰, Sorabh Lakhanpal¹¹, Ahmad O Babalghith¹², Eman Adnan Abu-Seer¹³, D Avinash¹⁴, Hassan A Alzahrani¹⁵, Abdulghani A Alhindi¹⁶, Danish Iqbal¹⁷, Sandeep Kumar¹⁸, Niraj Kumar Jha¹⁹, Saad Alghamdi²⁰

Affiliations

¹ Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, P.O. Box 59911, Abu Dhabi, United Arab Emirates.
² Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
³ Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Rajkot, Gujarat 360003, India.
⁴ Department of Biotechnology, GLA University, Mathura, Uttar Pradesh, India.
⁵ Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁶ Department of Neurology, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, India.
⁷ Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjeri, Mohali, Punjab 140307, India.
⁸ School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand.
⁹ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia.
¹⁰ Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia; Center for Health Research, Northern Border University, Arar, Saudi Arabia.
¹¹ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
¹² Medical Genetics Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
¹³ Department of Epidemiology and Medical Statistic, Faculty of Public Health and Health Informatics, Umm Al-Qura University, Makkah, Saudi Arabia.
¹⁴ Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India.
¹⁵ Department of Respiratory Care, Medical Cities at the Minister of Interior, MCMOl, Riyadh, Saudi Arabia.
¹⁶ Respiratory Care Unit, Security Forces Hospital, Makkah, Saudi Arabia.
¹⁷ Department of Health Information Management, College of Applied Medical Sciences, Buraydah Private Colleges, Buraydah 51418, Saudi Arabia.
¹⁸ School of Pharmacy, Sharda University, Greater Noida, India; DST-FIST Laboratory, Sharda University, Greater Noida, India.
¹⁹ Department of Biotechnology, School of Biosciences and Technology (SBT), Galgotias University, Greater Noida, India; Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura 140401, Punjab, India. Electronic address: nirajkumarjha2011@gmail.com.
²⁰ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.

PMID: 39419399
DOI: 10.1016/j.arr.2024.102548

Abstract

The complex pathophysiology of Alzheimer's disease (AD) poses challenges for the development of therapies. Recently, neuroinflammation has been identified as a key pathogenic mechanism underlying AD, while inflammation has emerged as a possible target for the management and prevention of AD. Several prior studies have demonstrated that medications modulating neuroinflammation might lessen AD symptoms, mostly by controlling neuroinflammatory signaling pathways such as the NF-κB, MAPK, NLRP3, etc, and their respective signaling cascade. Moreover, targeting these inflammatory modalities with inhibitors, natural products, and metabolites has been the subject of intensive research because of their anti-inflammatory characteristics, with many studies demonstrating noteworthy pharmacological capabilities and potential clinical applications. Therefore, targeting inflammation is considered a promising strategy for treating AD. This review comprehensively elucidates the neuroinflammatory mechanisms underlying AD progression and the beneficial effects of inhibitors, natural products, and metabolites in AD treatment.

Keywords: Alzheimer’s disease; MAPK; NF-κB; NLRP3; Neuroinflammation; Therapeutics.

Publication types

Review