Common Marker of Neurological Diseases May Play Role in Healthy Brains

Rendering of a synapse showing phosphorylated á-synuclein in pink “gluing” synaptic vesicles together.

Photo: ROY LAB/UCSD

Researchers have discovered that a protein called phosphorylated α-synuclein, which is associated with several neurodegenerative diseases such as Parkinson’s disease and Lewy body dementia, is also involved in the normal processes of how neurons communicate with each other in a healthy brain. 

The research, published in Neuron, was funded in part by NINDS.

Phosphorylation is a process where a phosphate ion is added to a specific amino acid, or building block of a protein, in this case the protein α-synuclein. This addition can change the shape of that protein, causing it to change its level of activity. 

Most studies of phosphoryl-synuclein have studied its role in certain neurological disorders such as Lewy body dementia, where it builds up in protein clumps called Lewy bodies. These clumps are thought to be toxic to neurons, and a prevailing hypothesis is that the phosphorylation of the protein α-synuclein triggers these diseases.

“In most studies to date, the mere presence of α-synuclein phosphorylation is assumed to be a marker for pathology for certain [neurological] disorders,” said Dr. Beth-Anne Sieber, NINDS program director. “Recently, there has been considerable interest in developing drugs that prevent α-synuclein phosphorylation as a way of treating these disorders. These findings challenge the current hypotheses about how these disorders may originate in the brain and may give insight into how we might better treat them.”