Neuronal inclusions in degenerative disorders - Do they represent static features or a key to understand the dynamics of the disease?

This brief paper analyzes a few degenerative diseases expressing as movement disorders and featuring at sub-cellular level the presence of neuronal inclusions in selective brain regions. We will first draw a short draft of representative neurological diseases featuring inclusion bodies by describing the type of inclusions occurring in various disorders and analyzing both common features and distinctive aspects. As a further step, we move from the bed to the bench side discussing recent developments obtained from experimental models of these disorders which shed new light into the cause and progression of neuronal inclusions, thus helping to understand the pathophysiology of neuronal degeneration underlying movement disorders. In line with this, we will focus oil recent studies which led to reproduce neuronal inclusions in vivo and in vitro by manipulating selective cellular structures/enzymatic pathways. In this way, we will try to encompass the dynamics of inclusion formation based on their fine ultrastructure and the analysis of the molecular components as well as their subcellular compartmentalization trying to relate the dynamics of inclusion formation and the pathophysiology of the disease process. An emphasis will be made on the ubiquitin proteasome system and Parkinson's disease where the analysis of neuronal inclusions enlightened potential therapeutic strategies to occlude the progression of this neuronal degeneration featured by movement disorders. (c) 2005 Elsevier Inc. All rights reserved.