Autophagy and the endo/exosomal pathways in health and disease

Abstract

Cell homeostasis requires the concerted action of cellular pathways involved in degradation, trafficking and intercellular communication, which are interlinked to satisfy the cell's needs upon demand. Defects in these pathways instigate the development of several age-related pathologies, such as neurodegenerative and chronic inflammatory diseases. Autophagy is an evolutionarily conserved and tightly regulated process of degrading cellular constituents. The endosomal and vesicular trafficking pathways contribute to this regulation and share common features with the autophagic process. Recently, autophagy has been implicated in the endosome/exosome secretory pathway. Importantly, current technological advances allow the manipulation of exosomes as drug nanocarriers in pharmaceutical intervention strategies. Here, we survey emerging findings relevant to the crosstalk between autophagy and the endo/exosomal vesicular trafficking pathways. In addition, we discuss novel methodologies that have recently been developed, which allow the utilization of these pathways for targeted drug delivery in disease.

Exosomal biomarkers in Down syndrome and Alzheimer's disease

“…As discussed in this review, toxic Aβ peptides and toxic species of P-Tau, neuroinflammation, and oxidative stress can all alter exosome content, secretion rate, and the cell-to-cell messages they carry. Several reports indicate that exosomes produced under pathological conditions can either confer protection or increased pathology to their target cells (Borland and Vilhardt 2017; Chiarini et al 2017; Goetzl et al 2016; Goetzl et al 2017; Kapogiannis et al 2015; Kouwaki et al 2016; Lee et al 2016; Li et al 2013; Papandreou and Tavernarakis 2017). Further study of these processes will provide new insights into how AD pathology spreads throughout the brain and the role of exosomes in this process.…”

“…Other groups have shown that not only autophagy, but also endosomal pathways, are hampered in both DS and AD, resulting in enlargement of early endosomes that significantly affects protein trafficking in the cytosol (Cataldo et al 2000; Cossec et al 2012) and may also ultimately affect the secretion and cargo of exosomes, as autophagy has been implicated in endosome/exosome secretory pathways (Papandreou and Tavernarakis 2017). Under conditions of perturbed membrane trafficking and lysosomal deficiency, such as in DS, pre-lysosomal compartments may instead fuse with the plasma membrane directly and release their toxic cargo components, and/or exosome secretion may be upregulated when lysosomal pathways are dysregulated (Borland and Vilhardt 2017).…”

Activation of autophagy in periodontal ligament mesenchymal stem cells promotes angiogenesis in periodontitis

“…It plays a regulating role not only in apoptosis and immune function, but also in differentiation and paracrine function . Notably, autophagy regulates secretion through autophagosomes . Autophagy also regulates angiogenesis.…”

“…PDLSCs autophagy can also be influenced by inflammation . Autophagy can regulate MSCs secretory function in certain conditions . Currently, most studies concerning autophagy‐related vascularization have focused on endothelial cell autophagy but few of them have taken the paracrine effects into consideration .…”

Malfunctions in synaptic membrane trafficking in early pathology of Parkinson’s disease: New molecular clues

“…Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of nigrostriatal neurons, which results in a triad of classical symptoms, such as resting tremor, rigidity and hypokinesia; these symptoms are followed by alterations in gait and balance and additional disturbances (Lotharius and Brundin, 2002;Cookson and Bandmann, 2010;Schulz-Schaeffer, 2012;Olanow and Brundin, 2013;Papandreou and Tavernarakis, 2017). Parkinson´s disease is one of the most common neurodegenerative diseases.…”