Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

• Published in: Amino acids Vol. 49; no. 7; pp. 1147 - 1157
• Main Authors: Morea, Veronica, Bidollari, Eris, Colotti, Gianni, Fiorillo, Annarita, Rosati, Jessica, De Filippis, Lidia, Squitieri, Ferdinando, Ilari, Andrea
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.07.2017; Springer Nature B.V
• Subjects: Analytical Chemistry; Biochemical Engineering; Biochemistry; Biological Transport, Active - genetics; Biomedical and Life Sciences; Brain; Brain - metabolism; Brain - pathology; Chorea; Coding; Death; Defects; Degeneration; energy intake; Energy levels; Energy Metabolism; Failure; genes; Glucose; Glucose - metabolism; Glucose transport; Humans; Huntingtin; Huntingtin Protein - genetics; Huntingtin Protein - metabolism; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Huntington's disease; Huntingtons disease; Hypometabolism; Impairment; Life Sciences; Metabolism; Motor task performance; Neostriatum; Neural coding; Neurobiology; Neurodegeneration; Neurodegenerative diseases; Neurons; nutrient transport; Patients; Polyglutamine; Proteomics; Review Article; Shade; Trinucleotide Repeat Expansion; Trinucleotide repeats; Weight loss; GLUT1; GLUT3; Glucose transport; Energetic metabolism; Huntington disease
• ISSN: 0939-4451; 1438-2199; 1438-2199
• DOI: 10.1007/s00726-017-2417-2

Huntington’s disease (HD) or Huntington’s chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.