Exosomes: Mediators of Neurodegeneration, Neuroprotection and Therapeutics

Abstract

Exosomes have emerged as prominent mediators of neurodegenerative diseases where they have been shown to carry disease particles such as beta amyloid and prions from their cells of origin to other cells. Their simple structure and ability to cross the blood-brain barrier allow great opportunity to design a “makeup” with drugs and genetic elements, such as siRNA or miRNA, and use them as delivery vehicles for neurotherapeutics. Their role in neuroprotection is evident by the fact that they are involved in the regeneration of peripheral nerves and repair of neuronal injuries. This review is focused on the role of exosomes in mediating neurodegeneration and neuroprotection.

Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain

“…There has been a growing realization that activated microglia play an integral role in synaptic remodeling, in part mediated by their capability to prune dendritic arbors and spines (23,24). Persistent inflammation caused by age and disease elicits chronic activation of microglia that can reshape the synaptic landscape and compromise cognition (24).…”

“…Persistent inflammation caused by age and disease elicits chronic activation of microglia that can reshape the synaptic landscape and compromise cognition (24). Mice depleted of microglia retain higher levels of dendritic spine density and suffer few if any adverse neurocognitive outcomes (25).…”

“…Although the mechanisms underlying the beneficial effects of stem cell transplantation are certain to be complex and multifaceted, present findings suggest that secreted MV likely play an important role in mediating trophic support derived from multipotent stem cells. MV contain a wealth of bioactive cargo ranging from long noncoding to micro-RNAs, neurotrophic factors, membrane-bound receptors, and other small molecules capable of playing a variety of neuromodulatory roles (23,24). These factors could directly or indirectly stimulate astroglial-derived plasticity or neuronal support through enhanced remyelination, neurogenesis, immunemodulation, the delivery of antioxidants, the secretion of neurotrophic factors, addition of membrane-bound receptors, the replenishment of neurotransmitter pools, or improved synaptic connectivity by attenuating intercellular signaling and the degradation of neuronal structure after irradiation (24).…”

Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells

“…Our previous studies have reported the rapid expulsion of biotinylated proteins from H9c2 cells following treatment with PMA or forskolin (Almami et al 2014). It could be that the rapid expulsion of biotinylated proteins from N2a cells occurs via exosomes (Kalani et al 2014). Since N2a cells secrete exosomes it will be interest to determine whether amine-labelled proteins can be detected in exosomes purified from cell culture supernatants obtained from these cells following PACAP-27 treatment (Chivet et al 2014).…”

First Demonstration of Transmissible Spongiform Encephalopathy-associated Prion Protein (PrPTSE) in Extracellular Vesicles from Plasma of Mice Infected with Mouse-adapted Variant Creutzfeldt-Jakob Disease by in Vitro Amplification

“…This finding opens new avenues for further TSE research. Because exosomes are known to not only participate in cell to cell communication processes (34,58,59,93), but to also cross the blood-brain barrier (94,95), association of PrP TSE with exosomes may serve as a platform for TSE spread from the periphery to the CNS (47,56,58). Additionally, we are further characterizing PrP TSE -bearing microvesicles with the goal of identifying the cellular origin of this protein in blood.…”