Weydt P, Dupuis L and Petersen Å.
Handbook of Clinical Neurology 157: 761-775 (2018)
Huntington disease (HD) is a paradigmatic autosomal-dominant adult-onset neurodegenerative disease. Since the identification of an abnormal expansion of a trinucleotide repeat tract in the huntingtin gene as the underlying genetic defect, a broad range of transgenic animal models of the disease has become available and these have helped to unravel the relevant molecular pathways in unprecedented detail. Of note, some of the most informative of these models develop thermoregulatory defects such as hypothermia, problems with adaptive thermogenesis, and an altered circadian temperature rhythm. Both central, e.g., in the hypothalamus and peripheral, i.e., the brown adipose tissue and skeletal muscle, problems contribute to the phenotype. Importantly, these structures and pathways are also affected in human HD. Yet, currently the evidence for bona fide thermodysregulation in human HD patients remains anecdotal. This may be due to a lack of reliable tools for monitoring body temperature in an outpatient setting. Regardless, study of the temperature phenotype has contributed to the identification of unexpected molecular targets, such as the PGC-1α pathway.