Parkinson's is a neurodegenerative disease with clinical manifestations that include motor (e.g., tremor and slowness in movements) as well as non-motor (e.g., sleep disorders and depression) symptoms. At the microscopic and pathological levels, the disease is characterized by accumulation of abnormal intraneuronal inclusions. They are formed as a result of aggregation of a protein called "alpha-synuclein." In the course of the disease, these inclusions progressively appear in various brain regions, contributing to the gradual exacerbation of disease severity. The mechanisms behind this advancing pathology are poorly understood. Research by DZNE scientists now indicates that "oxidative stress," i.e. an excessive and uncontrolled production of reactive oxygen species, could play an important role in the pathological spreading of alpha-synuclein. The findings are based on in-vivo studies with mice and in-vitro experiments in cultured cells.
"Oxidative stress has long been considered to be involved in the pathogenesis of Parkinson's disease. Our work, however, reveals a new intriguing mechanism that may link oxidative stress to disease development. We show that under oxidative stress the propensity of alpha-synuclein to 'travel' from one neuron to the other is significantly enhanced, thus facilitating the exchange of harmful protein species, occurrence of pathology and the spreading of this pathology throughout the brain," said Professor Donato Di Monte, a senior DZNE scientist, who headed the current research.
Study - Stress - Laboratory - Models - Production
He adds, "Although in our study we induced oxidative stress artificially in laboratory models, we know that increased production of deleterious oxygen species could occur in Parkinson's brain. It might be caused by a variety of conditions, such as genetic mutations and environmental exposures and might be related to the aging process itself, as some of the cellular mechanisms counteracting oxidative stress decline with age. Parkinson's is an age-related disease, making it quite likely that aging brain cells would become more vulnerable...
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