There was an article published yesterday in the online edition of Nature Communications’ by researchers in the Taub Institute at Columbia University Medical Centre. Asa Abeliovich, MD, PhD, the lead researcher and his colleagues, have identified a potential cause of non-familial Parkinson’s disease. The significance of this is that further research may be developed to prevent or slow the cause of this neuron destruction, as well as to design a blood test to detect the disease before clinical symptoms present.
It has been known that people with Parkinson’s disease acquire excess alpha-synuclein protein in the brain, which can damage neurons, especially dopamine producing neurons which are play an important role in controlling motor output and normal movement. What has not been known, is why this overdevelopment of alpha-synuclein protein occurs.
Abeliovich and his team used a variety of techniques, including gene-expression analysis and gene-network mapping and found that longer transcript forms of alpha-synuclein protein are the culprits. They were able to show that people with ‘bad’ variants of the gene make more of the elongated alpha-synuclein transcript forms. This ultimately means that more of the disease protein is made which can lead to accumulation of the protein in the brain and neuron destruction.
“Furthermore, we found that exposure to toxins associated with Parkinson’s can increase the abundance of this longer transcript form of alpha-synuclein. Thus, this mechanism may represent a common pathway by which environmental and genetic factors impact the disease,” said Dr. Abeliovich.
The findings suggest that drugs that reduce the accumulation of elongated alpha-synuclein transcripts in the brain might have therapeutic value in the treatment of Parkinson’s. The CUMC team is currently searching for drug candidates and has identified several possibilities.
The study also found elevated levels of the alpha-synuclein elongated transcripts in the blood of a group of patients with sporadic Parkinson’s, compared with unaffected controls. This would suggest that a test for alpha-synuclein may serve as a biomarker for the disease. “There is a tremendous need for a biomarker for Parkinson’s, which now can be diagnosed only on the basis of clinical symptoms. The finding is particularly intriguing, but needs to be validated in additional patient groups,” said Dr. Abeliovich. A biomarker could also speed clinical trials by giving researchers a more timely measure of a drug’s effectiveness.
Dr. Abeliovich’s paper is titled, “Alternative alpha-synuclein transcript usage as a convergent mechanism in Parkinson’s disease pathology.” The contributors are Herve Rhinn, Liang Qiang, Toru Yamashita , David Rhee, Ari Zolin, and William Vanti, all at CUMC.
The study was supported by the grants from the Michael J. Fox Foundation, the National Institutes of Health, and the National Institute of Neurological Disorders and Stroke (RO1NS064433).