Research
Role of intracytoplasmic neuronal inclusions in Parkinson’s Disease
From a neuropathological point of view, Parkinson’s disease (PD) is characterized not only by the loss of nigrostriatal dopaminergic neurons but also by the presence, in every affected brain region, of intraneuronal proteinacious cytoplasmic inclusions, called Lewy bodies (LBs). LBs classically appear in pigmented nigral neurons with hematoxylin/eosin staining as one or more eosinophilic spherical body with a dense core surrounded by a halo. LBs contain a variety of proteins, of which alpha-synuclein, a mutation in which gene was the first to be identified in a familial form of PD, is a major component.
Although LBs were first described by Friedrich Lewy in 1912, their complex ultrastructure and composition has remained unknown until relatively recently and their significance to the disease process is still a mystery. It has been postulated that LBs may be deleterious for neurons by deforming the cell and displacing important cell components or by interfering with protein function and intracellular trafficking. However, LBs may also represent a beneficial cellular response to remove harmful proteins from the cellular milieu. Alternatively, LBs may be just an epiphenomenon of the primary pathology and have little or no effect on neuronal viability.
Our group is interested in unraveling the significance and the mechanisms of LB formation in PD. The debate around the role of LBs may be of great therapeutic importance. If LBs are neurotoxic, then therapies preventing their formation may prove to be beneficial. In contrast, if LBs represent an adaptive or protective cellular response, then interfering with its formation could be harmful and accelerate the demise of vulnerable neurons. In any event, unraveling the mystery of LBs should certainly contribute to the understanding of the pathogenesis of PD and, therefore, to the development of new therapeutic tools for this devastating incurable illness.
Additional reading:
Genetic clues to the pathogenesis of Parkinson’s Disease.
Vila M. and Przedborski S.
Nature Medicine, 10 Suppl:S58-62 (2004)
