Following initial diagnosis of
Parkinson's disease, if it were possible to prescribe a treatment that could halt or prevent further neurodegeneration,
disease progression could be prevented. The aim of this study was to generate a quick and reliable assay for assessing putative
neuroprotective agents for parkinsonian patients. Abnormalities in mitochondria,
proteasome and lysosome function, as well as oxidative stress cause cell death in
Parkinson's disease. Thus, we exposed
neuroblastoma (SH-SY5Y) cells to EC(50) of toxins that mimic these cell death mechanisms (
dopamine to induce oxidative stress;
naphthazarin to inhibit lysosome function;
proteasome inhibitor N-carbobenzyloxy-Ile-Glu(O-t-butyl)-Ala-
leucinal (PSI) to inhibit the UPS (
ubiquitin proteasome system) and
rotenone to inhibit mitochondria function) in the presence of five compounds previously chosen as
neuroprotective agents, and assessed cell viability.
Coenzyme Q10 (117 μM) significantly protected against four toxins,
dopamine: 16.3 ± 3.3%;
naphthazarin: 10.8 ± 1.1%; PSI: 16.2 ± 2.9%;
rotenone: 53.2 ± 4.2%; whereas
caffeine (140 μM),
creatine (25 mM),
nicotine (1 μM) and
deprenyl (10 μM) provided protection against some, but not all toxins. Interestingly,
coenzyme Q10 is the only compound out of the five that showed neuroprotective potential in clinical trials. Thus, there is a direct correlation between the success of disease modifying agents in the clinic and their ability to protect against multiple cell death mechanisms in this assay. We propose that exposure of SH-SY5Y cells to different toxins that recapitulate cell death mechanisms in
Parkinson's disease serves as a rapid and reliable method to test
neuroprotective agents that may succeed in clinical trials.