Dear Colleagues, 

Axonal degeneration or axonopathy is a neurotoxic disorder in which the primary site of toxicity is the axon. Axonopathies involve alterations in the cytoskeleton and defects in axonal transport and represent a common starting point for neuronal pathological alterations across a very wide range of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. However, the molecular pathways that regulate this process are unknown.

Neurons have highly specialized structures for intercellular communication. In particular, axons transfer proteins and organelles over considerable distances throughout the nervous system. Furthermore, the constant quality of proteins and mitochondria is critical for correct neuronal function. Consequently, axonal transport is necessary to maintain neuronal homeostasis, which particularly depends on efficient degradation pathways such as the autophagy mechanism. As such, the precise investigation of autophagy in the soma, axons, or synapses would represent a beneficial therapeutic intervention to combat neurodegenerative diseases. Importantly, the pathological contribution of an over-activation of autophagy should also be monitored very carefully.

Lipids and lipid-metabolizing enzymes control fundamental aspects of the autophagy process, and lipids themselves have also been identified as autophagy substrates. In the process referred to as macrolipophagy, cellular fat such as triacylglycerides (TAG) is directly consumed (or broken down into fatty acids) in the form of lipid droplets (LDs) by autophagolysosomes for the purpose of energy homeostasis. In addition, cholesterol has been implicated in the organization of microdomains within lysosomal membranes that control the efficacy of chaperone-mediated autophagy as well as autophagosome–lysosome fusion.

LDs are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy. In addition to energy storage, LDs play other important functions, including sequestration of toxic proteins, protection from lipotoxicity, and provision of precursors for membrane biosynthesis, hormones, and lipoproteins. Notably, neurodegenerative diseases share lipid dysregulation as a metabolic feature in disease pathology.Hence, the knowledge of the convergent molecular mechanisms between axonal maintenance, autophagy, and lipid droplets is critical to combat neurodegenerative diseases. This Special Issue will collect papers focused on understanding the mechanisms relating autophagy to axonal damage in axonopathies in the context of lipid metabolism.

Dr. Esther Dalfó
Guest Editor

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• Axonopathy
• Autophagy
• Lipid metabolism
• Lipid droplets
• Neurodegeneration