18 Dec 2003

Since the discovery about a year ago that mutations in the DJ-1 protein can cause Parkinson's disease (see ARF related news story), speculation about the role of the protein has been rife (see ARF related news story). Now, the group that originally identified the Parkinson's mutations reveals that DJ-1 may also play a role in the formation of neurofibrillary tangles found in Alzheimer's (AD) and of similar bodies found in other neurodegenerative diseases.

In the Early View of Annals of Neurology online, the international group, including Peter Heutink from the Erasmus Medical Center, Rotterdam; John Trojanowski from the University of Pennsylvania School of Medicine, Philadelphia; and their colleagues from elsewhere in The Netherlands, Italy, and the USA, report that DJ-1 is found in tauopathies, or intracellular inclusions that consist largely of the tau protein.

First author Patricia Rizzu made the connection by probing sections from the Amsterdam and Philadelphia brain bank collections with both polyclonal and monoclonal antibodies against DJ-1. When Rizzu examined sections from a variety of diseases with known tauopathies, the DJ antibodies stained the bodies to various extents. For example, in all six cases of Pick's disease (PiD) tested DJ-1 was detected in the Pick bodies. In six of eight AD cases, DJ was found in neurofibrillary tangles (though weakly in one case), and in four of five cases of Lewy body variant of AD, the protein appeared in neuropil threads. DJ was also found to associate with tau in dementia with Lewy bodies, corticobasal degeneration, frontotemporal dementia with Parkinsonism linked to chromosome 17, and progressive supranuclear palsy.

The significance of these associations remains to be elucidated. Nonetheless, DJ-1 sequestration in such inclusion bodies could contribute to neurodegeneration in various ways, depending on the true function of the protein. As DJ-1 may be crucial for transcription, its loss could affect gene regulation. Or, if it primarily functions as an antioxidant, then its accumulation in intracellular inclusions may leave the cell susceptible to oxidative damage.

Whatever the role of the DJ, the authors suggest that their latest data lends "credence to the emerging idea that seemingly 'distinct' neurodegenerative diseases may have critical, common underlying pathological mechanisms."—Tom Fagan