Role for nanomaterial-autophagy interaction in neurodegenerative disease. Autophagy 4:1097-1100

Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
Autophagy (Impact Factor: 11.75). 12/2008; 4(8):1097-100. DOI: 10.4161/auto.7142
Source: PubMed


Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nanotechnology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated elevated levels of autophagic vacuoles upon exposure of cells to certain nanomaterials, including carbon- and metal-based nanoparticles. While this apparent increase in autophagic activity may be an appropriate cellular response toward nanomaterial clearance, often the interaction between nanomaterials and the autophagy pathway is disruptive, resulting in severe morphological changes and coincident cell death. Interestingly, epidemiological studies have identified an association between exposure to combustion-derived ambient particles (which are predominantly nanoscale) and neurological conditions with Alzheimer's and Parkinson's disease-like pathologies. Becuse impaired autophagy may play an important role in the pathogenesis of these and other diseases, it is intriguing to speculate about the plausible involvement of nanoscale particulates in this process. The interaction of nanomaterials with the autophagy pathway, and the potential negative consequences of resulting autophagy dysfunction, should be explored further.

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    • "It has been reported that some nanoparticles such as nanoscale carbon black, fullerene, nanoscale neodymium oxide could induce autophagic cell death [16]. On the other hand, nanomaterials such as fullerene derivative may impede autophagy by causing lysosomal disorders, such as lysosome localization and enzyme inhibiting [17]. Autophagy functions as a tumor suppression mechanism by removing damaged organelles/proteins and limiting cell growth and genomic instability [18] [19]. "
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    • "In searching for new emerging mechanisms of action of NM toxicity, recent literature data strongly highlight the roles of autophagy and lysosomal dysfunction [58]. Most likely, autophagy induction may be used to degrade NMs, perceived by the cell as foreign body, via sequestration into autophagosomes [59]. Several papers suggest that this interaction could be exploited in cancer management. "
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    • "Disruption in autophagosome trafficking to the lysosome has also been implicated in neurodegenerative diseases, such as mutant dynactin associated motor neuron disease and amyotrophic lateral sclerosis, as well as myopathies, such as inclusion body myopathy [33]. As exposure to airborne pollution has been associated with Alzheimer and Parkinson-like pathologies, and nanoparticles are the primary particle number and surface area component of pollution-derived particulates, we (S.T.S.) have recently postulated a relationship between nanoparticle-induced autophagy dysfunction and pollution-associated neurodegeneration [2]. In support of this hypothesis, autophagy dysfunction has recently been postulated as a mechanism of manganese nanoparticle-induced cytotoxicity in dopaminergic neuronal cells [79]. "
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    ABSTRACT: The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.
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