Miro1 deficiency in amyotrophic lateral sclerosis.
Proper transportation of mitochondria to sites with high energy demands is critical for neuronal function and survival. Impaired mitochondrial movement has been repeatedly reported in motor neurons of amyotrophic lateral sclerosis (ALS) patients and indicated as an important mechanism contributing t...
| Published in: | Frontiers in Aging Neuroscience Vol. 7; pp. 1 - 9 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Published: |
Frontiers Media S.A.
May2015
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103550884&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103550884 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16634365 BG2U jtl: Frontiers in Aging Neuroscience issn: 16634365 maglogo: N pubinfo: dt: May2015 vid: 7 pid: 40038 pub: Frontiers Media S.A. artinfo: ui: 103550884 10.3389/fnagi.2015.00100 103550884 ppf: 1 ppct: 8 formats: tig: atl: Miro1 deficiency in amyotrophic lateral sclerosis. aug: au: Fan Zhang Wenzhang Wang Siedlak, Sandra L. Yingchao Liu Jun Liu Keji Jiang Perry, George Xiongwei Zhu Xinglong Wang affil: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA sug: ab: Proper transportation of mitochondria to sites with high energy demands is critical for neuronal function and survival. Impaired mitochondrial movement has been repeatedly reported in motor neurons of amyotrophic lateral sclerosis (ALS) patients and indicated as an important mechanism contributing to motor neuron degeneration in ALS. Miro1, a RhoGTPase also referred to as Rhot1, is a key regulator of mitochondrial movement linking mitochondria and motor proteins. In this study, we investigated whether the expression of Miro1 was altered in ALS patients and ALS animal models. Immunoblot analysis revealed that Miro1 was significantly reduced in the spinal cord tissue of ALS patients. Consistently, the decreased expression of Miro1 was also noted only in the spinal cord, and not in the brain tissue of transgenic mice expressing ALSassociated SOD1 G93A or TDP-43 M337V. Glutamate excitotoxicity is one of the major pathophysiological mechanisms implicated in the pathogenesis of ALS, and we found that excessive glutamate challenge lead to significant reduction of Miro1 expression in spinal cord motor neurons both in vitro and in mice. Taken together, these findings show Miro1 deficiency in ALS patients and ALS animal models and suggest glutamate excitotoxicity as a likely cause of Miro1 deficiency. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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