Parkinson’s disease is a progressive neurodegenerative disorder that affects more than 10 million people worldwide. The neuropathological hallmarks of Parkinson’s disease are the loss of dopamine-producing neurons in the substantia nigra region of the brain and the aggregation of alpha synuclein, a type of protein. People who have Parkinson’s disease experience both motor symptoms (such as tremors and a shuffling gait) and non-motor symptoms (such as pain, fatigue, and difficulty concentrating or remembering). Findings from a new study suggest that people with Parkinson’s disease have defects that promote poor blood-brain barrier function, impairing angiogenesis and autophagy.

The blood-brain barrier is a lining of epithelial (skin-like) cells that exchanges nutrients, waste, and signaling molecules. The integrity of the blood-brain barrier relies on angiogenesis,the process by which new blood vessels form in response to various cell signaling molecules and growth factors. Autophagy also supports epithelial health by sequestering protein aggregates, pathogens, and damaged or dysfunctional organelles so they can be broken down and re-used. It performs both a general housekeeping role and a targeted cleansing strategy to maintain cellular health. Autophagy is impaired in Parkinson’s disease, reducing clearance of alpha synuclein aggregates and driving neuronal death.

The investigators previously found that nilotinib, a drug commonly used to treat chronic myelogenous leukemia, halted some of the motor and non-motor symptoms of Parkinson’s disease. The current study clarified the mechanisms that drove these improvements by analyzing cerebrospinal microRNAs, small, non-coding RNA molecules that play important roles in regulating gene expression. Previous research has identified abnormal levels of microRNAs that control genes associated with autophagy in the cerebrospinal fluid of people with Parkinson’s disease. These microRNAs drive the upregulation of proteins that promote degradation of the blood-brain barrier.

The investigators randomly assigned 75 people with Parkinson’s disease to receive 150 or 300 milligrams of nilotinib or a placebo every day for a year. They collected cerebrospinal fluid samples from the participants at the end of the year and conducted genetic sequencing of RNA that they had isolated in the fluid.

They found that after participants were on nilotinib for one year, their cerebrospinal fluid levels of microRNAs that control genes and pathways involved in angiogenesis, autophagy, and collagen (a component of the blood-brain-barrier) increased, and their symptoms improved. Participants who received the placebo did not experience these changes and improvements.

These findings demonstrate that people with Parkinson’s disease have altered expression of genes involved in blood-brain-barrier integrity and autophagy. They further indicate that addressing vascular defects associated with Parkinson’s disease may be beneficial in treating some of the symptoms that accompany the disorder.

• Link to full publication.

• Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.