Autophagy and Parkinson's disease: A love-hate relationship

J.M. Fuentes, J.M.B.-S. Pedro, R. Gómez-Sánchez, M. Niso-Santano, R.A. González-Polo



Parkinson's disease (PD) is a disorder characterized by a progressive degeneration of midbrain neurons in the substantia nigra and by the presence of cytoplasmic protein inclusions. Therefore, the pathogenesis of this disease has been linked to dysfunctions of cellular degradation. The etiology of this disease is unknown, although it seems clear that the pathogenesis involves a multifactorial process combining genetic predisposition (mutations, deletions, etc.) and exposition to certain environmental factors. Autophagic dysfunction is emerging as an important topic in the study of neurodegenerative diseases in which appears aggregated proteins, including PD. Autophagy involves the sequestration of portions of the cytoplasm (cytosol and/or organelles) in structures called autophagosomes and their subsequent lysosomal enzyme degradation. Although, some early studies identified the autophagy as a mechanism of cell death, in recent years it is placing value as a process by which cells can adapt to changes and stress, including nutrient deprivation, hypoxia, DNA damage, mitochondrial alterations or endoplasmic reticulum stress, among others. In this sense, it has recently demonstrated that genetic ablation of autophagy in mice induces neurodegeneration and accumulation of ubiquitinated proteins. In addition, some genetic mutations that cause neurodegenerative diseases can directly affect the proteolytic systems responsible for the degradation of the mutant protein. In PD, the death of dopaminergic neurons in the substantia nigra is associated with the accumulation of α-synuclein, which has synaptic functions within inclusions called Lewy bodies. Reflecting a multifactorial disease process, the pattern of cell death in PD is complex, with characteristics of apoptosis and necrosis as well as accumulations autophagosome-like structures. Interestingly, different types of mutant genes that trigger familial PD encode proteins that act in ubiquitin-dependent proteasomal system, underlining the pathogenic importance of failure of proteolysis in PD. Furthermore, various parkinsonian-related toxicants have been shown to impair mitochondrial function, redox balance, and to some extent protein degradation machinery. The knowledge of the role of autophagy in the pathogenesis of PD and the study of the regulation of the interaction between environmental agents and genes mutations can open new lines of research to improve human health and the clarification of different alternatives therapeutic potential of PD. © 2012 by Nova Science Publishers, Inc. All rights reserved.
Originele taal-2English
StatusPublished - 2012
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'Autophagy and Parkinson's disease: A love-hate relationship'. Samen vormen ze een unieke vingerafdruk.

Citeer dit