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      Type 2 Diabetes (T2DM) and Parkinson’s Disease (PD): a Mechanistic Approach

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          Abstract

          Growing evidence suggest that there is a connection between Parkinson’s disease (PD) and insulin dysregulation in the brain, whilst the connection between PD and type 2 diabetes mellitus (T2DM) is still up for debate. Insulin is widely recognised to play a crucial role in neuronal survival and brain function; any changes in insulin metabolism and signalling in the central nervous system (CNS) can lead to the development of various brain disorders. There is accumulating evidence linking T2DM to PD and other neurodegenerative diseases. In fact, they have a lot in common patho-physiologically, including insulin dysregulation, oxidative stress resulting in mitochondrial dysfunction, microglial activation, and inflammation. As a result, initial research should focus on the role of insulin and its molecular mechanism in order to develop therapeutic outcomes. In this current review, we will look into the link between T2DM and PD, the function of insulin in the brain, and studies related to impact of insulin in causing T2DM and PD. Further, we have also highlighted the role of various insulin signalling pathway in both T2DM and PD. We have also suggested that T2DM-targeting pharmacological strategies as potential therapeutic approach for individuals with cognitive impairment, and we have demonstrated the effectiveness of T2DM-prescribed drugs through current PD treatment trials. In conclusion, this investigation would fill a research gap in T2DM-associated Parkinson’s disease (PD) with a potential therapy option.

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          Parkinson disease

          Werner Poewe, Klaus Seppi, Caroline M Tanner … (2017)
          Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.
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            Global estimates of diabetes prevalence for 2013 and projections for 2035.

            L Guariguata, D.R. Whiting, I Hambleton … (2014)
            Diabetes is a serious and increasing global health burden and estimates of prevalence are essential for appropriate allocation of resources and monitoring of trends. We conducted a literature search of studies reporting the age-specific prevalence for diabetes and used the Analytic Hierarchy Process to systematically select studies to generate estimates for 219 countries and territories. Estimates for countries without available source data were modelled from pooled estimates of countries that were similar in regard to geography, ethnicity, and economic development. Logistic regression was applied to generate smoothed age-specific prevalence estimates for adults 20-79 years which were then applied to population estimates for 2013 and 2035. A total of 744 data sources were considered and 174 included, representing 130 countries. In 2013, 382 million people had diabetes; this number is expected to rise to 592 million by 2035. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries. Estimates will be updated annually including the most recent, high-quality data available. Copyright © 2013. Published by Elsevier Ireland Ltd.
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              The pathobiology of diabetic complications: a unifying mechanism.

              M. Brownlee (2005)
              Article 0 comments Cited 545 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Balachandar Vellingiri:
                ORCID: http://orcid.org/0000-0002-3043-6839
                geneticbala@buc.edu.in
                Journal
                Journal ID (nlm-ta): Mol Neurobiol
                Journal ID (iso-abbrev): Mol Neurobiol
                Title: Molecular Neurobiology
                Publisher: Springer US (New York )
                ISSN (Print): 0893-7648
                ISSN (Electronic): 1559-1182
                Publication date (Electronic): 28 April 2023
                Pages: 1-27
                Affiliations
                [1 ]GRID grid.428366.d, ISNI 0000 0004 1773 9952, Department of Zoology, School of Basic Sciences, , Stem Cell and Regenerative Medicine/Translational Research, Central University of Punjab (CUPB), ; Bathinda, 151401 Punjab India
                [2 ]GRID grid.411677.2, ISNI 0000 0000 8735 2850, Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, , Bharathiar University, ; Coimbatore, 641 046 Tamil Nadu India
                [3 ]GRID grid.412055.7, ISNI 0000 0004 1774 3548, Department of Biotechnology, , Karpagam Academy of Higher Education (Deemed to Be University), ; Coimbatore, 641021 Tamil Nadu India
                [4 ]GRID grid.412813.d, ISNI 0000 0001 0687 4946, Department of Biomedical Sciences, School of Biosciences and Technology, , Vellore Institute of Technology (VIT), ; Vellore, 632 014 India
                [5 ]GRID grid.411677.2, ISNI 0000 0000 8735 2850, Department of Zoology, , Bharathiar University, ; Coimbatore, 641 046 Tamil Nadu India
                [6 ]GRID grid.411813.e, ISNI 0000 0000 9217 3865, Department of Biotechnology, , Mizoram University (A Central University), ; Aizawl, 796004 Mizoram India
                Author information
                http://orcid.org/0000-0002-3043-6839
                Article
                Publisher ID: 3359
                DOI: 10.1007/s12035-023-03359-y
                PMC ID: 10144908
                PubMed ID: 37118323
                SO-VID: 59a1cf26-1c5f-48c5-9d13-0a5e3644c5c7
                Copyright © © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) 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.
                License:

                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.

                History
                Date received : 30 January 2023
                Date accepted : 19 April 2023
                Funding
                Funded by: Indian Council of Medical Research-DHR
                Award ID: GIA/2019/000276/PRCGIA
                Award Recipient :
                Categories
                Subject: Article

                ScienceOpen disciplines: Neurosciences
                Keywords: parkinson’s disease,type 2 diabetes mellitus,insulin,pathophysiology,therapeutics
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: parkinson’s disease, type 2 diabetes mellitus, insulin, pathophysiology, therapeutics

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