Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders

Huan      Cai; Wei-na      Cong; Sunggoan      Ji; Sarah      Rothman; Stuart      Maudsley; Bronwen      Martin

doi:10.2174/156720512799015064

Abstract

Alzheimers 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 Alzheimers disease, Huntingtons disease, and Parkinsons 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.

Keywords: Neurodegenerative diseases, metabolic dysfunction, bodyweight, diabetes, glucose homeostasis, insulin, leptin, ghrelin, adiponectin, glucagon-like peptide 1, Alzheimer's disease, Huntington's disease, Parkinson's disease