Membrane trafficking illuminates a path to Parkinson’s disease

Takafumi Hasegawa, Naoto Sugeno, Akio Kikuchi, Toru Baba, Masashi Aoki

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that is characterized by progressive movement disability and a variety of non-motor symptoms. The neuropathology of PD consists of the loss of dopaminergic neurons in the midbrain and the appearance of neuronal inclusions called Lewy bodies, which contain insoluble α-synuclein, a relatively small protein originally identified in association with synaptic vesicles in the presynaptic nerve terminals. Drugs that replenish dopamine can partly alleviate the motor symptoms, but they do not cure the disease itself. Therefore, there is an urgent need for disease modification in terms of the delay or prevention of neurodegeneration. Recent advances in genetic and biochemical studies have provided unifying conceptual frameworks of the pathogenesis of PD. Particularly, membrane trafficking has aroused special attention as an initiator or enhancer of the neurodegenerative process that leads to PD. Defects in the cellular trafficking pathway result in synaptic dysfunction and the accumulation of misfolded α-synuclein. Likewise, changes in intracellular sorting and degradation profoundly influence the cellular trafficking of misfolded proteins, thereby facilitating the cell-to-cell spreading of hazardous α-synuclein species in a prion-like manner. Here, we will review our current knowledge of the functional roles of membrane trafficking in PD and will discuss how this cellular process could induce or facilitate the functional and pathological alterations in this disease.

Original languageEnglish
Pages (from-to)63-76
Number of pages14
JournalTohoku Journal of Experimental Medicine
Volume242
Issue number1
DOIs
Publication statusPublished - 2017 May
Externally publishedYes

Keywords

  • Lewy body
  • Membrane trafficking
  • Parkinson’s disease
  • Prion-like propagation
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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