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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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      The Role of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) in Diabetes-Related Neurodegenerative Diseases

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          Abstract

          Recent clinical guidelines have emphasized the importance of screening for cognitive impairment in older adults with diabetes, however, there is still a lack of understanding about the drug therapy. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used in the treatment of type 2 diabetes and potential applications may include the treatment of obesity as well as the adjunctive treatment of type 1 diabetes mellitus in combination with insulin. Growing evidence suggests that GLP-1 RA has the potential to treat neurodegenerative diseases, particularly in diabetes-related Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here, we review the molecular mechanisms of the neuroprotective effects of GLP-1 RA in diabetes-related degenerative diseases, including AD and PD, and their potential effects.

          Most cited references229

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          Type 2 diabetes.

          Melanie Davies, Sudesna Chatterjee, Kamlesh Khunti (2017)
          415 million people live with diabetes worldwide, and an estimated 193 million people have undiagnosed diabetes. Type 2 diabetes accounts for more than 90% of patients with diabetes and leads to microvascular and macrovascular complications that cause profound psychological and physical distress to both patients and carers and put a huge burden on health-care systems. Despite increasing knowledge regarding risk factors for type 2 diabetes and evidence for successful prevention programmes, the incidence and prevalence of the disease continues to rise globally. Early detection through screening programmes and the availability of safe and effective therapies reduces morbidity and mortality by preventing or delaying complications. Increased understanding of specific diabetes phenotypes and genotypes might result in more specific and tailored management of patients with type 2 diabetes, as has been shown in patients with maturity onset diabetes of the young. In this Seminar, we describe recent developments in the diagnosis and management of type 2 diabetes, existing controversies, and future directions of care.
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            Crosstalk of reactive oxygen species and NF-κB signaling.

            Michael J. Morgan, Zheng-gang Liu (2011)
            NF-κB proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-κB also plays important roles in other processes, including development, cell growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain NF-κB-regulated genes play a major role in regulating the amount of ROS in the cell, ROS have various inhibitory or stimulatory roles in NF-κB signaling. Here we review the regulation of ROS levels by NF-κB targets and various ways in which ROS have been proposed to impact NF-κB signaling pathways.
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              Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

              Aaron M Koenig, Shannon L. Macauley-Rambach, Zoe Arvanitakis … (2018)
              Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 14 March 2022
                Publication date Collection: 2022
                Volume: 16
                Pages: 665-684
                Affiliations
                [1 ]Department of Endocrinology and Metabolism, The First Hospital of Jilin University , Changchun, 130021, People’s Republic of China
                Author notes
                Correspondence: Guixia Wang; Xue Zhao, Department of Endocrinology and Metabolism, The First Hospital of Jilin University , Changchun, 130021, People’s Republic of China, Tel +86 15843081103; +86 18744014213, Email gwang168@jlu.edu.cn; xuezhao@jlu.edu.cn
                Article
                Publisher ID: 348055
                DOI: 10.2147/DDDT.S348055
                PMC ID: 8943601
                PubMed ID: 35340338
                SO-VID: 520cb3f6-56fb-42a9-ab1b-506f073213e0
                Copyright © © 2022 Cheng et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 05 November 2021
                Date accepted : 18 February 2022
                Page count
                Figures: 1, Tables: 3, References: 229, Pages: 20
                Categories
                Subject: Review

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: glucagon-like peptide-1,diabetes mellitus,alzheimer’s disease,parkinson’s disease,cognition
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: glucagon-like peptide-1, diabetes mellitus, alzheimer’s disease, parkinson’s disease, cognition

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