Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model.
BACKGROUND
Overexpression and abnormal accumulation of aggregated alpha-synuclein (alphaS) have been linked to Parkinson's disease (PD) and other synucleinopathies. alphaS can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase alphaS aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction and oxidative damage in PD cell models.


RESULTS
Here we show that curcumin can alleviate alphaS-induced toxicity, reduce ROS levels and protect cells against apoptosis. We also show that both intracellular overexpression of alphaS and extracellular addition of oligomeric alphaS increase ROS which induces apoptosis, suggesting that aggregated alphaS may induce similar toxic effects whether it is generated intra- or extracellulary.


CONCLUSIONS
Since curcumin is a natural food pigment that can cross the blood brain barrier and has widespread medicinal uses, it has potential therapeutic value for treating PD and other neurodegenerative disorders.
Wang
Min S
MS
Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287-6006, USA.
Boddapati
Shanta
S
Emadi
Sharareh
S
Sierks
Michael R
MR
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity
D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D003474:Curcumin