Editorial: Golgi Pathology in Neurodegenerative Diseases

The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway sustaining the delivery of proteins from their site of synthesis in the endoplasmic reticulum to their final destination, the extracellular medium, the plasma membrane, and the endo-lysosomal system. It ensures post-translational protein modifications such as glycosylation and proteolytic cleavage and processing and acts as a sorting device including to neuronal axons and dendrites (Horton and Ehlers, 2003; Ye et al., 2007). The mammalian Golgi apparatus was first described by Camillo Golgi in 1998 as " apparato reticolare interno, " " a fine and elegant network within the cell body. .. completely internal in the nerve cells " (Golgi, 1898a,b). This large reticulum comprises stacks of flattened membrane bound compartments called cisternae which are laterally linked to form the so-called Golgi ribbon. Structural and functional alterations of the Golgi apparatus, which are here collectively termed Golgi pathology, are now recognized as a constant pathological hallmark of various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Parkinson, Alzheimer, Huntington, and prion diseases (Fan et al., 2008). In ALS, structural Golgi alterations have been revealed by the pioneering work of Gonatas and colleagues (Mourelatos et al., 1990; Gonatas et al., 1992; Fujita et al., 2002). They manifest as fragmentation—transformation of the Golgi ribbon into disconnected stacks, cisternae, tubules and vesicles, and as atrophy—loss of Golgi membrane material. These morphological changes are often accompanied by functional Golgi alterations, such as those affecting the anterograde and retrograde transport in the early secretory pathway, both in At least in ALS, Golgi pathology manifests as an early pre-clinical feature in degenerating neurons both in affected patients and in animal models (Mourelatos et al., 1996), suggesting that it may be relevant to the disease process instead of just representing an epiphenomenon. Yet, neither the molecular mechanisms underlying the changes in the functional organization of the Golgi apparatus nor their precise relevance to neurodegeneration have yet been completely elucidated. These important questions got a new boost by the discovery of mutations in genes encoding Golgi-related proteins as direct causes of neurodegeneration. For instance, mutations in Optineurin (Maruyama et al., 2010), VPS54/wobbler (Schmitt-John et al., 2005), and TBCE/pmn (Martin et al., 2002) have been identified in ALS and related motor neuron diseases. Furthermore, mutations in the Parkinson disease-associated proteins α-Synuclein (Cooper et al., 2006;