title: Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q.
abstract: Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been hypothesized to participate in the pathology of neurodegenerative diseases. The systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of selective striatal lesions. However, it remains unclear whether specific neurons are selectively targeted in 3-NP-infused striatal degeneration. Recently, it has been proposed that complement-mediated synapse elimination may be reactivated aberrantly in the pathology of neurodegenerative diseases. We hypothesized that ASK1 is involved in striatal astrocyte reactivation; reactive astrocyte secretes molecules detrimental to neuron; and striatal neurons are more susceptible to these factors. Our results indicate that striatal astrocyte is reactivated and ASK1 level increases after 3-NP general and chronic infusion. Reactive striatal astrocyte increases TGF-beta differentially to cortex and striatum. ASK1 may be involved in regulation of astrocyte TGF-beta and it is linked to the C1q level in spatial and temporal, and moreover in the earlier stage of progressing striatal neuronal loss. Conclusively the present study suggests that ASK1 mediates 3-NP toxicity and regulates C1q level through the astrocyte TGF-beta. And also it may suggest that C1q level may be a surrogate of prediction marker representing neurodegenerative disease progress before developing behavioral impairment.
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea.
authors.forename: Kyoung Joo
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: Department of Anesthesiology and Pain, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Cheon
authors.affiliation: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea.
authors.forename: Gyung Whan
authors.initials: GW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death; D015922:Complement C1q / Q000276:immunology*; D003342:Corpus Striatum / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005786:Gene Expression Regulation; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009574:Nitro Compounds / Q000009:adverse effects; D011422:Propionates / Q000009:adverse effects; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D009574:Nitro Compounds; D011422:Propionates; D011951:Receptors, Complement; D053773:Transforming Growth Factor beta1; C032402:complement 1q receptor; D015922:Complement C1q; D048848:MAP Kinase Kinase Kinase 5; C015392:3-nitropropionic acid