Background

Parkinson’s Disease

Parkinson’s Disease is a chronic neurological disorder named after Dr. James Parkinson, who first described it 1817. It results from a loss of dopaminergic (dopamine producing) neurons from the substantia nigra, an area of the lower brain. This primarily affects voluntary controlled movement.
- There is no medical test to diagnose Parkinson’s disease.
- Nearly 100 000 Canadians have Parkinson’s disease and its current national economic impact is approximately $23 per Canadian, per year.
- The prolonged use of most currently available drugs can result in adverse side effects, such as dyskinesia (involuntary muscle contractions).
- Although the cause of Parkinson’s disease is still not clear, researchers are highly optimistic about making a breakthrough that might lead to a better treatment or cure for Parkinson’s disease in the next 10 to 15 years.

Apoptosis and Parkinson’s Disease

Various studies have measured the levels of apoptotic molecules in the substantia nigra of Parkinson’s disease patients and all have shown that the levels are significantly increased. This indicates that apoptosis may have a significant role in the pathology of Parkinson’s disease.

Guanosine

Guanosine is a nucleoside formed from the nucleic acid guanine and a ribose ring. It is a nonadenine-based purine with many neurotrophic and neuroprotective effects.

Although guanosine does not reach the brain in substantial amounts by ingestion, synthetic purine derivatives such as AIT-082 have been created which do cross the blood-brain barrier.

Guanosine has substantial potential as a therapeutic treatment for many types of brain trauma including strokes and neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Research has also shown that guanosine is anti-apoptotic in Alzheimer’s disease in vitro.

Alpha-Synuclein

One of the chief characteristics of Parkinson’s Disease is the formation of Lewy bodies, protein aggregates consisting of mainly of α-synuclein.

The protein α-synuclein is extremely toxic to dopaminergic neurons. When it aggregates abnormally α-synuclein triggers the self-destruction of a cell through apoptosis. Impairment of α-synuclein degradation was recently proposed as the mechanism for elevation of cellular concentrations of α-synuclein, aggregate formation, and neurotoxicity.

Alpha-synuclein has also been detected in several other neurodegenerative diseases including cortical Lewy body dementia and ALS.

MPP+

MPP+ is the toxic metabolite of MPTP. It causes rapid-onset Parkinson’s disease symptoms in humans. MPP+ is now used as an animal model to mimic Parkinson’s disease.

MPP+ induces α-synuclein aggregation which is considered to be one of the key features of Parkinson’s disease and it specifically targets dopaminergic neurons.

Human SH-SY5Y Neuroblastoma Cells