Does Parkinsonism begin before birth?
500,000 people are diagnosed with Parkinson's disease every year in the United States. Most patients are 60 or older at the time of diagnosis, but about 10% become ill between the ages of 21 and 50.
A research team from Cedars-Sinai Medical Center, California, USA, studied induced pluripotent stem cells (iPSCs) created from cells of young patients with Parkinson's disease. This process returns adult blood cells to a "primitive" embryonic state.
Dopamine neurons were created from the obtained iPSCs, cultured in vitro and analyzed for the ability to perform their function.
This technique allowed us to assess how well the neurons could function from the very beginning of the patient's life.
Researchers have discovered two key abnormalities of dopamine neurons:
1. Accumulation of alpha-synuclein protein, which occurs in most forms of Parkinson's disease.
2. Malfunctioning lysosomes are structures that must destroy and remove unnecessary proteins from the cell. This malfunction can lead to the accumulation of alpha-synuclein.
These changes cause the first signs of Parkinson's disease. Most likely, dopamine neurons in these people may continue to incorrectly utilize alpha-synuclein for 20 or 30 years, causing the gradual appearance of symptoms of Parkinson's disease.
The researchers also used simulated neurons to test a number of drugs that could reverse the observed disorders. They found that the drug PEP005, approved for the treatment of precancerous skin conditions, reduced elevated levels of alpha-synuclein in dopamine neurons both in vitro and in mice.
The drug also counteracted another anomaly that was detected – an increased level of the active version of the enzyme protein kinase C, but its role in the development of Parkinson's disease is not clear.
As for the next steps, the team plans to investigate how PEP005, currently available in gel form, can be delivered to the brain for potential treatment or prevention of Parkinson's disease in young patients. It is also planned to conduct additional studies to determine whether the abnormalities found in cells in patients with early onset of Parkinson's disease are characteristic of patients with other forms of Parkinsonism.
The article by A.H.Laperle et al. iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates published in the journal Nature Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Cedars-Sinai: Parkinson's Disease May Start Before Birth.