Dysfunction of Protein Quality control in Parkinsonism-Dementia complex of Guam

Bert M. Verheijen*, Kiyomitsu Oyanagi, Fred W. van Leeuwen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Article number173
Number of pages8
JournalFrontiers in Neurology
Volume9
DOIs
Publication statusPublished - 20 Mar 2018

Keywords

  • Guam parkinsonism-dementia complex
  • mutant ubiquitin
  • protein quality control
  • protein aggregation
  • tau
  • neurofibrillary tangles
  • 43-kDa TAR DNA-binding protein
  • neuropathology
  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • UBIQUITIN-PROTEASOME SYSTEM
  • ALPHA-SYNUCLEIN PATHOLOGY
  • MUTANT UBIQUITIN
  • ALZHEIMERS-DISEASE
  • NEURODEGENERATIVE DISEASES
  • NEUROFIBRILLARY TANGLES
  • TERMINAL HYDROLASE
  • ABERRANT UBIQUITIN
  • INCLUSION-BODIES

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