In struggling to find the cause of Parkinsons disease, scientists have recently homed in on a mysterious protein called alpha-synuclein. Researchers suspect abnormal activity of alpha-synuclein is involved not only in inherited, but also in non-inherited forms of the devastating disease. In the January issue of Genome Research, Robert Nussbaum and colleagues from the National Institutes of Health use information on human and mouse genomes to uncover a novel genetic element that controls alpha-synuclein activity.
Mutations in the alpha-synuclein gene cause some cases of inherited Parkinsons. In addition, deposits of alpha-synuclein protein are found in Lewy bodies, the protein aggregates found in the brains of Parkinsons patients. For these reasons, scientists suspect that even common, non-inherited forms of Parkinson's may involve abnormal gene activity or damage to the protein itself. To pinpoint factors that influence alpha-synuclein function, Nussbaum and colleagues looked for DNA sequences in the human genome that can control alpha-synuclein gene activity. They compared the region of the human genome containing alpha-synuclein to its equivalent region in mouse, reasoning that sequences common to both species represent important genetic elements. The comparison identified several potential control elements for alpha-synuclein. Nussbaum and colleagues found that removing one such element (NACP-REP1) greatly diminishes gene activity, indicating the identified elements may indeed be important for the normal (and abnormal) functioning of this Parkinson's-related protein.