Parkinson's disease is one of the most common neurodegenerative disorder that is slowly progressive and manifested by muscle rigidity, tremor, decreased mobility and postural instability. The disease is caused by a combination of genetic and environmental factors.
The most prominent pathological features are the severe loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of cytoplasmic protein inclusions called Lewy bodies, primarily composed of fibrillar α-synuclein and ubiquitinated proteins within some remaining nigral neurons. Autophagy is a catabolic process that maintain cellular homeostasis, through the selection of misfolded proteins, damaged organelles, and even pathogenic organisms to be degraded by lysosomes. Autophagy can mediate cytoprotection (for instance neuroprotection and cardioprotection in the context of ischemic preconditioning) and delay the pathogenic manifestations of aging. Dysregulation of autophagy has been observed in the brain tissues from Parkinson’s disease patients and animal models. In recent years, some reports have shown a new relationship between macroautophagy and lipid metabolism. In this work, we used the most consumed polyunsaturated fatty acid in our diet, linoleic acid, to evaluate if it induces autophagy and if there is a possible relationship between linoleic acid-induced autophagy and the neuroprotective/toxic mechanisms triggered by this compound. We found that linoleic acid induces autophagy at concentrations equal or higher than 200 μM, and we describe its activation pathway, using Western blotting and immunofluorescence assays. Our results suggest that linoleic acid-activated autophagy process is mammalian target of rapamycin-independent, class III phosphatidylinositol 3-kinase/Beclin1-independent and AMP-activated protein kinase-dependent. As for the neuroprotective capacity of linoleic acid, we observed that alone it shows some toxicity. However, if co-administered with an inducer of reactive oxygen species (such as paraquat), linoleic acid does not increase paraquat toxicity. On the other hand, when linoleic acid is co-administered with puromycin (protein aggregates generator) it has a neuroprotective effect
