Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease

Subbiah Pugazhenthi, Limei Qin, P. Hemachandra Reddy

    Research output: Contribution to journalArticle

    112 Scopus citations

    Abstract

    Cognitive decline in chronic diabetic patients is a less investigated topic. Diabetes and obesity are among the modifiable risk factors for Alzheimer's disease (AD), the most common form of dementia. Studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation that are observed in these disorders. Advanced glycation end products generated by chronic hyperglycemia and their receptor RAGE provide critical links between diabetes and AD. Peripheral inflammation observed in obesity leads to insulin resistance and type 2 diabetes. Although the brain is an immune-privileged organ, cross-talks between peripheral and central inflammation have been reported. Damage to the blood brain barrier (BBB) as seen with aging can lead to infiltration of immune cells into the brain, leading to the exacerbation of central inflammation. Neuroinflammation, which has emerged as an important cause of cognitive dysfunction, could provide a central mechanism for aging-associated ailments. To further add to these injuries, adult neurogenesis that provides neuronal plasticity is also impaired in the diabetic brain. This review discusses these molecular mechanisms that link obesity, diabetes and AD. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases — edited by P. Hemachandra Reddy.

    Original languageEnglish (US)
    Pages (from-to)1037-1045
    Number of pages9
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1863
    Issue number5
    DOIs
    StatePublished - May 1 2017

    Keywords

    • Advanced glycation end products
    • Alzheimer's disease
    • Diabetes
    • Inflammation
    • Mitochondria
    • Obesity
    • Oxidative stress

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology

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