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dc.contributor.authorHu, Kurt
dc.contributor.authorGaire, Bhakta Prasad
dc.contributor.authorSubedi, Lalita
dc.contributor.authorArya, Awadhesh
dc.contributor.authorTeramoto, Hironori
dc.contributor.authorLiu, Chunli
dc.contributor.authorHu, Bingren
dc.date.accessioned2021-10-21T12:19:35Z
dc.date.available2021-10-21T12:19:35Z
dc.date.issued2021-09-28
dc.identifier.urihttp://hdl.handle.net/10713/16895
dc.description.abstractA typical neuron consists of a soma, a single axon with numerous nerve terminals, and multiple dendritic trunks with numerous branches. Each of the 100 billion neurons in the brain has on average 7,000 synaptic connections to other neurons. The neuronal endolysosomal compartments for the degradation of axonal and dendritic waste are located in the soma region. That means that all autophagosomal and endosomal cargos from 7,000 synaptic connections must be transported to the soma region for degradation. For that reason, neuronal endolysosomal degradation is an extraordinarily demanding and dynamic event, and thus is highly susceptible to many pathological conditions. Dysfunction in the endolysosomal trafficking pathways occurs in virtually all neurodegenerative diseases. Most lysosomal storage disorders (LSDs) with defects in the endolysosomal system preferentially affect the central nervous system (CNS). Recently, significant progress has been made in understanding the role that the endolysosomal trafficking pathways play after brain ischemia. Brain ischemia damages the membrane fusion machinery co-operated by N-ethylmaleimide sensitive factor (NSF), soluble NSF attachment protein (SNAP), and soluble NSF attachment protein receptors (SNAREs), thus interrupting the membrane-to-membrane fusion between the late endosome and terminal lysosome. This interruption obstructs all incoming traffic. Consequently, both the size and number of endolysosomal structures, autophagosomes, early endosomes, and intra-neuronal protein aggregates are increased extensively in post-ischemic neurons. This cascade of events eventually damages the endolysosomal structures to release hydrolases leading to ischemic brain injury. Gene knockout and selective inhibition of key endolysosomal cathepsins protects the brain from ischemic injury. This review aims to provide an update of the current knowledge, future research directions, and the clinical implications regarding the critical role of the neuronal endolysosomal trafficking pathways in ischemic brain injury.en_US
dc.description.urihttps://doi.org/10.3389/fnmol.2021.719100en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Molecular Neuroscienceen_US
dc.rightsCopyright © 2021 Hu, Gaire, Subedi, Arya, Teramoto, Liu and Hu.en_US
dc.subjectN-ethylmaleimide sensitive fusion proteinen_US
dc.subjectautophagic fluxen_US
dc.subjectautophagosomeen_US
dc.subjectbrain ischemia-reperfusion injuryen_US
dc.subjectcathepsin Ben_US
dc.subjectearly endosomeen_US
dc.subjectlate endosomeen_US
dc.subjectmembrane traffickingen_US
dc.titleInterruption of Endolysosomal Trafficking After Focal Brain Ischemiaen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fnmol.2021.719100
dc.identifier.pmid34650402
dc.source.volume14
dc.source.beginpage719100
dc.source.endpage
dc.source.countrySwitzerland


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