martes, 5 de febrero de 2019

Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease | Translational Neurodegeneration | Full Text

Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease | Translational Neurodegeneration | Full Text

Translational Neurodegeneration

Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease

Translational Neurodegeneration20198:6
  • Received: 24 August 2018
  • Accepted: 14 January 2019
  • Published: 

Abstract

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain areas. The detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear, and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in PD. However, the formation of α-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD, possibly stemming from the consequence of protein misfolding and dysfunctional proteostasis. Proteostasis is the mechanism for maintaining protein homeostasis via modulation of protein translation, enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and autophagy. Deregulated protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes, leading to pathological protein aggregation and neurodegeneration in PD. In recent years, multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been identified. The potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

Keywords

  • Molecular targets
  • Neuron degeneration
  • Parkinson’s disease
  • Protein aggregation
  • Protein translation
  • Proteostasis

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