Huntington's disease: the current state of research with peripheral tissues.
Huntington's disease (HD) is a genetically dominant condition caused by expanded CAG repeats. These repeats code for a glutamine tract in the HD gene product huntingtin (htt), which is a protein expressed in almost all tissues. Although most HD symptoms reflect preferential neuronal death in specific brain regions, even before the HD gene was identified numerous reports had described additional abnormalities in the peripheral tissues of HD patients, including weight loss, altered glucose homeostasis, and sub-cellular abnormalities in fibroblasts, lymphocytes and erythrocytes. Several years have elapsed since the HD mutation was discovered, and analyses of peripheral tissues from HD patients have helped to understand the molecular pathogenesis of the disease and revealed that the molecular mechanisms through which mutated htt leads to cell dysfunction are widely shared between central nervous system (CNS) and peripheral tissues. These studies show that in peripheral tissues, mutated htt causes accumulation of intracellular protein aggregates, impairment of energetic metabolism, transcriptional deregulation and hyperactivation of programmed cell-death mechanisms. Here, we review the current knowledge of peripheral tissue alterations in HD patients and in animal models of HD and focus on how this information can be used to identify potential therapeutic possibilities and biomarkers for disease progression.
Sassone
Jenny
J
Department of Neurology and Laboratory of Neuroscience, Dino Ferrari Center, IRCCS Istituto Auxologico Italiano, University of Milan Medical School, via Spagnoletto 3, 20149, Milan, Italy.
Colciago
Clarissa
C
Cislaghi
Giuliana
G
Silani
Vincenzo
V
Ciammola
Andrea
A
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004700:Endocrine System Diseases / Q000209:etiology; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000209:etiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000503:physiopathology; D012106:Research; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
D009419:Nerve Tissue Proteins