Research Topic

Golgi Pathology in Neurodegenerative Diseases

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The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway sustaining the delivery of signal sequence bearing proteins from their site of synthesis in the endoplasmic reticulum to their final destination, the extracellular medium and the plasma membrane. The mammalian Golgi ...

The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway sustaining the delivery of signal sequence bearing proteins from their site of synthesis in the endoplasmic reticulum to their final destination, the extracellular medium and the plasma membrane. The mammalian Golgi apparatus comprises stacks of flattened membrane bound compartments called cisternae. Golgi stacks are further linked laterally to form a large reticulum, the Golgi ribbon. This organelle functions in post-translational protein modifications (in glycosylation and proteolytic cleavage) as well as a sorting device.

Neurodegeneration, such as in amyotrophic lateral sclerosis (ALS), Parkinson (PD) and Alzheimer disease (AD) is characterised by irreversible protein aggregates as well as an early occurence of Golgi pathology. This is characterised by Golgi fragmentation and atrophy that are defined by the transformation of the Golgi ribbon into disconnected elements, and by the loss of Golgi membrane material, respectively. Although these features are consistant hallmarks of degenerating neurons in patients, animal models and cell culture, the molecular mechanisms of Golgi pathology and its relevance to neurodegeneration remain unclear.

These important questions get a new boost by the recent discovery of ALS genes encoding Golgi proteins and PD genes modifying Golgi function, the recognition of Golgi-derived microtubules and their specific functions, and the better understanding of Golgi transport processes. Furthermore, some of the features of neurogeneration resemble those imposed by cellular stress suggesting that they could be linked. To cover these emerging themes, articles focusing on the following issues are welcome in this Frontiers Research Topic

I : Golgi pathology in neurodegenerative diseases.
We aim at providing a comprehensive overview on the mechanisms and functional relevance of Golgi pathology in neurons and describe specific features of Golgi fragmentation associated with ALS-linked mutations in SOD1, TDP43, Optineurin, autosomal dominant SMA linked to BICD2, PD and AD.

II. Defective microtubules or microtubule-associated proteins cause Golgi pathology
Manuscripts will focus on the role of Golgi-derived microtubules and Golgi outposts, in particular their nucleation and dynamics, their role in determining neuronal shape, and their interaction with Dyneins and related motor proteins.

III. Golgi pathology induced by altered formation, transport or tethering of Golgi vesicles
Submitted articles will explain how defective crosstalk between vesicle trafficking and tubulin polymerization causes Golgi fragmentation in pmn mice and how defective GARP-dependent retrograde transport is linked to Golgi fragmentation in wobbler mice mutated in Vps54. In addition, the question of how ALS-linked Profilin 1 gene mutations impact on cytoskeleton, Golgi and stress granules will be addressed.

IV. The Golgi apparatus as a trigger of neuronal degeneration
Cell death pathways initiated at the Golgi will be summarized. Articles in this collection will also highlight how mutations in FIG4 impede phospholipid-dependent trafficking in Charcot-Marie Tooth disease CMT4J and how mutations in Seipin/BSCL2 (Berardinelli-Seip congenital lipodystrophy type 2) cause Golgi fragmentation and degeneration of motor neurons.

V. The Golgi under stress. A link to neurodegeneration
We will describe the feature of cellular stress responses to the Golgi in term of functional organisation, including this imposed by nutrient and oxidative stress, DNA damage, genotoxic stress, as well as virus infection.
We will draw a link to neurodegeneration.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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