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Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease.

Abstract

The pathophysiological link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been suggested in several reports. Few findings suggest that T2DM has strong link in the development process of AD, and the complete mechanism is yet to be revealed. Formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two central hallmarks in the AD. APs are the dense composites of β-amyloid protein (Aβ) which accumulates around the nerve cells. Moreover, NFTs are the twisted fibers containing hyperphosphorylated tau proteins present in certain residues of Aβ that build up inside the brain cells. Certain factors contribute to the aetiogenesis of AD by regulating insulin signaling pathway in the brain and accelerating the formation of neurotoxic Aβ and NFTs via various mechanisms, including GSK3β, JNK, CamKII, CDK5, CK1, MARK4, PLK2, Syk, DYRK1A, PPP, and P70S6K. Progression to AD could be influenced by insulin signaling pathway that is affected due to T2DM. Interestingly, NFTs and APs lead to the impairment of several crucial cascades, such as synaptogenesis, neurotrophy, and apoptosis, which are regulated by insulin, cholesterol, and glucose metabolism. The investigation of the molecular cascades through insulin functions in brain contributes to probe and perceive progressions of diabetes to AD. This review elaborates the molecular insights that would help to further understand the potential mechanisms linking T2DM and AD.

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  • Authors+Show Affiliations

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    Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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    Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia, aditya.arya@taylors.edu.my. Department of Pharmacology and Therapeutics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia, aditya.arya@taylors.edu.my. Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Bukit Gambir, Gelugor, Pulau Pinang, Malaysia, aditya.arya@taylors.edu.my.

    ,

    Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia, aditya.arya@taylors.edu.my.

    ,

    School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.

    ,

    School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.

    ,

    School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.

    School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.

    Source

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Animals
    Diabetes Mellitus, Type 2
    Humans
    Insulin Resistance
    Neurofibrillary Tangles

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    30538427

    Citation

    Rad, Sima Kianpour, et al. "Mechanism Involved in Insulin Resistance Via Accumulation of Β-amyloid and Neurofibrillary Tangles: Link Between Type 2 Diabetes and Alzheimer's Disease." Drug Design, Development and Therapy, vol. 12, 2018, pp. 3999-4021.
    Rad SK, Arya A, Karimian H, et al. Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease. Drug Des Devel Ther. 2018;12:3999-4021.
    Rad, S. K., Arya, A., Karimian, H., Madhavan, P., Rizwan, F., Koshy, S., & Prabhu, G. (2018). Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease. Drug Design, Development and Therapy, 12, pp. 3999-4021. doi:10.2147/DDDT.S173970.
    Rad SK, et al. Mechanism Involved in Insulin Resistance Via Accumulation of Β-amyloid and Neurofibrillary Tangles: Link Between Type 2 Diabetes and Alzheimer's Disease. Drug Des Devel Ther. 2018;12:3999-4021. PubMed PMID: 30538427.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease. AU - Rad,Sima Kianpour, AU - Arya,Aditya, AU - Karimian,Hamed, AU - Madhavan,Priya, AU - Rizwan,Farzana, AU - Koshy,Shajan, AU - Prabhu,Girish, Y1 - 2018/11/22/ PY - 2018/12/13/entrez PY - 2018/12/13/pubmed PY - 2019/3/27/medline KW - Alzheimer’s disease KW - cholesterol KW - insulin deficiency KW - insulin signaling pathway KW - type 2 diabetes mellitus SP - 3999 EP - 4021 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 12 N2 - The pathophysiological link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been suggested in several reports. Few findings suggest that T2DM has strong link in the development process of AD, and the complete mechanism is yet to be revealed. Formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two central hallmarks in the AD. APs are the dense composites of β-amyloid protein (Aβ) which accumulates around the nerve cells. Moreover, NFTs are the twisted fibers containing hyperphosphorylated tau proteins present in certain residues of Aβ that build up inside the brain cells. Certain factors contribute to the aetiogenesis of AD by regulating insulin signaling pathway in the brain and accelerating the formation of neurotoxic Aβ and NFTs via various mechanisms, including GSK3β, JNK, CamKII, CDK5, CK1, MARK4, PLK2, Syk, DYRK1A, PPP, and P70S6K. Progression to AD could be influenced by insulin signaling pathway that is affected due to T2DM. Interestingly, NFTs and APs lead to the impairment of several crucial cascades, such as synaptogenesis, neurotrophy, and apoptosis, which are regulated by insulin, cholesterol, and glucose metabolism. The investigation of the molecular cascades through insulin functions in brain contributes to probe and perceive progressions of diabetes to AD. This review elaborates the molecular insights that would help to further understand the potential mechanisms linking T2DM and AD. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/30538427/Mechanism_involved_in_insulin_resistance_via_accumulation_of_β_amyloid_and_neurofibrillary_tangles:_link_between_type_2_diabetes_and_Alzheimer's_disease_ L2 - https://dx.doi.org/10.2147/DDDT.S173970 DB - PRIME DP - Unbound Medicine ER -