Dysfunction of Protein Quality Control in Parkinsonism–Dementia Complex of Guam

• Main Authors: Bert M. Verheijen, Kiyomitsu Oyanagi, Fred W. van Leeuwen
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-03-01
• Series: Frontiers in Neurology
• Subjects: Guam parkinsonism–dementia complex; mutant ubiquitin; protein quality control; protein aggregation; tau; neurofibrillary tangles
• Online Access: http://journal.frontiersin.org/article/10.3389/fneur.2018.00173/full

Guam parkinsonism–dementia complex (G-PDC) is an enigmatic neurodegenerative disease that is endemic to the Pacific island of Guam. G-PDC patients are clinically characterized by progressive cognitive impairment and parkinsonism. Neuropathologically, G-PDC is characterized by abundant neurofibrillary tangles, which are composed of hyperphosphorylated tau, marked deposition of 43-kDa TAR DNA-binding protein, and neuronal loss. Although both genetic and environmental factors have been implicated, the etiology and pathogenesis of G-PDC remain unknown. Recent neuropathological studies have provided new clues about the pathomechanisms involved in G-PDC. For example, deposition of abnormal components of the protein quality control system in brains of G-PDC patients indicates a role for proteostasis imbalance in the disease. This opens up promising avenues for new research on G-PDC and could have important implications for the study of other neurodegenerative disorders.