Impulse control disorder, lysosomal malfunction and ATP13A2 insufficiency in Parkinsonism

Jun-Ping Liu, Jianfeng Li, Yanhua Lu, Lihui Wang, Gang Chen

Research output: Contribution to journalReview ArticleOtherpeer-review

2 Citations (Scopus)

Abstract

Lysosomal transport of cargos in neurons is essential for neuronal proteostasis, transmission and functional motors and behaviours. Lysosomal malfunction including storage disorders is involved in the pathogenesis of Parkinson's disease (PD). Given the unclear molecular mechanisms of diverse defects in PD phenotypes, especially behavioural deficits, this mini review explores the cellular contexts of PD impulse control disorders and the molecular aspects of lysosomal cross-membrane transports. Focuses are paid to trace metal involvements in α-synuclein assembly in Lewy bodies, the functions and molecular interactions of ATP13A2 as ATPase transporters in lysosomal membranes for cross-membrane trafficking and lysosomal homeostasis, and our current understandings of the neural circuits in ICD. Erroneously polarized distributions of cargos such as metals and lipids on each side of lysosomal membranes triggered by gene mutations and deregulated expression of ATP13A2 may thus instigate sensing protein structural changes such as aggregations, organelle degeneration, and specific neuronal ageing and death in Parkinsonism.

Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume44
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • hypersexuality
  • impulse control disorder
  • lysosome transport
  • skin picking
  • trace metals
  • trichotillomania

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