Article

Pan, T., Kondo, S., Le, W. & Jankovic, J. The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 131, 1969-1978

Parkinson's Disease Research Laboratory, Baylor College of Medicine, Houston, TX 77030, USA.
Brain (Impact Factor: 9.2). 02/2008; 131(Pt 8):1969-78. DOI: 10.1093/brain/awm318
Source: PubMed

ABSTRACT

The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are the two most important mechanisms that normally repair or remove abnormal proteins. Alterations in the function of these systems to degrade misfolded and aggregated proteins are being increasingly recognized as playing a pivotal role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease. Dysfunction of the UPS has been already strongly implicated in the pathogenesis of this disease and, more recently, growing interest has been shown in identifying the role of ALP in neurodegeneration. Mutations of alpha-synuclein and the increase of intracellular concentrations of non-mutant alpha-synuclein have been associated with Parkinson's disease phenotype. The demonstration that alpha-synuclein is degraded by both proteasome and autophagy indicates a possible linkage between the dysfunction of the UPS or ALP and the occurrence of this disorder. The fact that mutant alpha-synucleins inhibit ALP functioning by tightly binding to the receptor on the lysosomal membrane for autophagy pathway further supports the assumption that impairment of the ALP may be related to the development of Parkinson's disease. In this review, we summarize the recent findings related to this topic and discuss the unique role of the ALP in this neurogenerative disorder and the putative therapeutic potential through ALP enhancement.

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Available from: Joseph Jankovic, Mar 29, 2015
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    • "As known, Parkinson's disease (PD) is resulted by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) of midbrain (Bae et al., 2011). Preventing aggregated and misfolded proteins in brain blocked the progression of PD which may propose a potential therapeutic benefi t (Pan et al., 2008a; Bae et al., 2011). Recently, the ubiquitin-proteasome system and the autophagy-lysosomal pathway are the two most important cellular mechanisms for protein degradation (Pan et al., 2008b). "
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