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A perspective on recent findings and future strategies for reactive aldehyde removal in spinal cord injury

Neural Regeneration Research 2023年第10期18卷 2190-2191页

作者： seth a.herr Anna J.Prall Riyi Shi Center for Paralysis Research Purdue UniversityWest LafayetteINUSA Department of Basic Medical Sciences College of Veterinary MedicinePurdue UniversityWest LafayetteINUSA Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteINUSA

Acrolein in spinal cord injury:The propensity of reactive aldehydes such as acrolein to both initiate and perpetuate tissue damage after spinal cord injury (SCI) is well *** primarily from lipid peroxidation,acrolein is known to be one of the most reactive *** will quickly overwhelm endogenous clearance mechanisms and antioxidants,and form adductswith lipids,proteins,and DNA.

关键词： aldehydes finding primarily

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Critical role of mitochondrial aldehyde dehydrogenase 2 in acrolein sequestering in rat spinal cord injury

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Neural Regeneration Research 2022年第7期17卷 1505-1511页

作者： seth a.herr Liangqin Shi Thomas Gianaris Yucheng Jiao Siyuan Sun Nick Race Scott Shapiro Riyi Shi Center for Paralysis Research&Department of Basic Medical Sciences College of Veterinary MedicinePurdue UniversityWest LafayetteINUSA Department of Orthopedics Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityInstitute of Trauma and OrthopedicsShanghaiChina Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA

Lipid peroxidation-derived aldehydes,such as acrolein,the most reactive aldehyde,have emerged as key culprits in sustaining post-spinal cord injury(SCI)secondary pathologies leading to functional *** evidence suggests that mitochondrial aldehyde dehydrogenase-2(ALDH2),a key oxidoreductase and powerful endogenous anti-aldehyde machinery,is likely important for protecting neurons from aldehydesmediated *** a rat model of spinal cord contusion injury and recently discovered ALDH2 activator(Alda-1),we planned to validate the aldehyde-clearing and neuroprotective role of *** an acute 2 day period post injury,we found that ALDH2 expression was significantly lowered post-SCI,but not so in rats given *** lower enzymatic expression may be linked to heightened acrolein-ALDH2 adduction,which was revealed in co-immunoprecipitation *** have also found that administration of Alda-1 to SCI rats significantly lowered acrolein in the spinal cord,and reduced cyst *** addition,Alda-1 treatment also resulted in significant improvement of motor function and attenuated post-SCI mechanical hypersensitivity up to 28 days ***,ALDH2 was found to play a critical role in in vitro protection of PC12 cells from acrolein *** is expected that the outcome of this study will broaden and enhance anti-aldehyde strategies in combating post-SCI neurodegeneration and potentially bring treatment to millions of SCI *** animal work was approved by Purdue Animal Care and Use Committee(approval No.1111000095)on January 1,2021.

关键词： acrolein acrolein-lysine adduct alda-1 enzymatic catalyst lipid peroxidation mitochondrial aldehyde dehydrogenase-2 neurotrauma oxidative stress reactive aldehydes spinal cord contusion

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Acrolein scavenger dimercaprol offers neuroprotection in an animal model of Parkinson’s disease:implication of acrolein and TRPA1

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Translational Neurodegeneration 2021年第2期10卷 151-165页

作者： Liangqin Shi Yazhou Lin Yucheng Jiao seth Aherr Jonathan Tang Edmond Rogers Zhengli Chen Riyi Shi College of Basic Medicine Chengdu University of Traditional Chinese MedicineChengdu 610075China Center for Paralysis Research&Department of Basic Medical Sciences College of Veterinary MedicinePurdue UniversityWest LafayetteIN 47907USA Laboratory of Animal Disease Model College of Veterinary MedicineSichuan Agricultural UniversityChengdu 625014China Department of Orthopedics Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityInstitute of Trauma and OrthopedicsShanghai 200025China Weldon School of Biomedical Engineering Purdue University West LafayetteWest LafayetteIN 47907USA

Background:The mechanisms underlying lesions of dopaminergic(DA)neurons,an essential pathology of Parkinson’s disease(PD),are largely unknown,although oxidative stress is recognized as a key *** have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology,and that acrolein scavenger hydralazine can reduce the elevated acrolein,mitigate DA neuron death,and alleviate motor deficits in a 6-hydroxydopamine(6-OHDA)rat *** such,we hypothesize that a structurally distinct acrolein scavenger,dimercaprol(DP),can also offer neuroprotection and behavioral ***:DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA *** acrolein levels and related pathologies were measured by *** and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod *** was assessed using mechanical allodynia,cold hypersensitivity,and plantar ***,the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to ***:DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1(TRPA1)channels in the substantia nigra,striatum,and *** also mitigated both motor and sensory deficits typical of *** addition,DP lowered acrolein and protected DA-like cells in ***’s ability to upregulate TRPA1 was also verified in vitro using cell ***:These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in *** the extensive involvement of acrolein in various nervous system illnesses and beyond,anti-acrolein strategies may have wide applications and broad impacts on human health.

关键词： Oxidative stress Parkinson’s disease Neuroinflammation Acrolein TRPA1 Dimercaprol

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