Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders

Metabolism Unit, National Institute on Aging, Baltimore, MD 21224, USA.
Current Alzheimer research (Impact Factor: 3.89). 01/2012; 9(1):5-17. DOI: 10.2174/156720512799015064
Source: PubMed


Alzheimer's disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer's disease, Huntington's disease, and Parkinson's disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and 'eumetabolic' activities may possess superior efficacies compared to less pluripotent remedies.

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    • "Despite this, research exploration in this regard has been limited, and there is evidence in the literature supporting this hypothesis. In this regard, obesity induced by diet has also been found to promote NADPH oxidase-associated oxidative stress in rat brains (Bishop et al., 2010; Golden and Melov, 2001; Zhang et al., 2005), indicating that brain oxidative stress could potentially mediate the pathogenesis of overnutrition-related metabolic diseases (Cai et al., 2012). In the present work, we found increased ROS and MDA as lipoperoxidation products. "
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    • "Importantly, beyond its effects on the circadian system and hippocampal dependent memory, ghrelin may also have potential for preventing or treating neurodegenerative disease. Neurodegenerative disorders often display coexisting metabolic dysfunction, and there are several converging lines of evidence linking metabolic syndromes with an increased risk of developing AD (Naderali et al., 2009; Kapogiannis and Mattson, 2011; Cai et al., 2012). For example, there is a growing literature suggesting that insulin deficiency and insulin resistance act as mediators of AD-type neurodegeneration. "
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    Frontiers in Aging Neuroscience 09/2014; 6. DOI:10.3389/fnagi.2014.00234 · 4.00 Impact Factor
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    • "Consequently, MetS has been considered as a risk factor for the development of cardiovascular diseases, type 2 diabetes mellitus (T2DM), and a number of dementias such as AD in patients over age 75 years (27). This is also reflected by the cellular and biochemical alterations observed in MetS since some of them have also been observed in AD patients (27, 28). In addition to MetS, insulin resistance in peripheral tissues corresponds to one of the main syndromes in T2DM and constitutes a high risk factor of developing AD (35). "
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