Alpha-synuclein (also α-synuclein) is a protein whose function in the healthy brain is currently unknown. It is of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies, protein clumps that are the pathological hallmark of Parkinson's disease.
In the several years since its discovery, alpha-synuclein has been the focus of intensive efforts by basic Parkinson's disease researchers working to definitively characterize the protein's role in Parkinson's and its potential as a target for neuroprotective therapies. Despite this, there are still more questions than answers as to whether and how alpha-synuclein plays a direct causative role in Parkinson's disease.
What is the latest research into the role that alpha-synuclein plays in Parkinson's disease?
There is compelling evidence from recent studies that alpha-synuclein may play a role in the development of both (rare) familial and (more common) sporadic cases of Parkinson's disease.
For a very small subset of Parkinson's patients, hereditary variability in the alpha-synuclein gene contributes to developing the disease. In these rare cases of familial Parkinson's disease, the alpha-synuclein gene produces either too much alpha-synuclein protein or an abnormal form of the protein — unusual events believed by some researchers to be toxic to brain cells and to result in neuron dysfunction.
Furthermore, alpha-synuclein is the primary structural component of Lewy bodies, suggesting that protein aggregation plays a role in sporadic Parkinson's disease as well.
These findings support the development of Parkinson's disease therapies that reduce alpha-synuclein gene expression or block its aggregation. Such therapies could potentially prevent or delay the onset of Parkinson's disease, or halt or slow its progression.
What's more, alpha-synuclein pathology has been found to exist in some body systems not traditionally associated with Parkinson's disease, as well as in patients who did not experience any clinical features of Parkinson's. For this reason, study of alpha-synuclein is crucial to test the emerging hypothesis that Parkinson's disease affects many areas of the central nervous system beyond the substantia nigra, and even extends beyond the boundaries of the central nervous system. This hypothesis has gained attention in recent years as appreciation has grown for the diversity of the clinical features of Parkinson's disease.
Finally, research is ongoing to determine whether alpha-synuclein may have a potential use as a biomarker of Parkinson's disease.
A vaccine approach targeting alpha-synuclein in Parkinson's patients is now in the clinic. The vaccine candidate, from Austrian biotech AFFiRiS, works by binding to alpha-synuclein and subsequently clearing it from the brain. It is now in the first stages of clinical testing.
Other approved compounds that have been shown to stop synuclein clumping, and to break up existing clumps, are moving forward in pre-clinical testing.
As of January 2012, The Michael J. Fox Foundation had invested over $47 million in projects targeting alpha-synuclein.