Amyotrophic lateral sclerosis-associated toxic exosomes (ALS-exosomes) (ALS-exosomes)

Amyotrophic lateral sclerosis-associated toxic exosomes (ALS-exosomes) are specialized extracellular vesicles, typically 30–150 nm in diameter, that are secreted by neurons and glial cells and play a pivotal role in the pathogenesis of ALS (Basso et al., 2013). These vesicles encapsulate and transport neurotoxic cargo, including misfolded proteins such as TDP-43, SOD1, and FUS, as well as pathogenic microRNAs, from diseased cells to healthy neighboring cells (Iguchi et al., 2016). This mechanism facilitates the prion-like propagation of protein aggregates throughout the central nervous system, which is a hallmark of disease progression (Silverman et al., 2019). Furthermore, these toxic exosomes can induce inflammatory responses in microglia and astrocytes, creating a neurotoxic environment that further accelerates motor neuron death (Pinto et al., 2017). From a therapeutic perspective, ALS-exosomes are being targeted through the inhibition of their biogenesis using small molecules like GW4869 or through the development of antibodies designed to neutralize them in the extracellular space (Gomes et al., 2020). They also represent significant potential as liquid biopsy biomarkers, as their molecular contents reflect the pathological state of the central nervous system (Thompson et al., 2020).

Other names

ALS-derived extracellular vesiclesALS-EVsPathogenic extracellular vesicles in ALSTDP-43-containing exosomes

Inhibition of neutral sphingomyelinase 2 (nSMase2) to reduce exosome biogenesis; blockade of Rab GTPase-mediated vesicle secretion; antibody-mediated sequestration and clearance of circulating toxic vesicles