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Tau Pathology Triggered by Spinal Cord Injury Can Play a Critical Role in the Neurotrauma Development

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Abstract

Traumatic spinal cord injury (SCI) can result in substantial neurological impairment along with significant emotional and psychological distress. It is clear that there is profound neurodegeneration upon SCI, gradually spread to other spinal cord regions and brain areas. Despite extensive considerations, it remains uncertain how pathogenicity diffuses in the cord. It has been reported that tau protein abnormal hyperphosphorylation plays a central role in neurodegeneration triggered by traumatic brain injury (TBI). Tau is a microtubule-associated protein, heavily implicated in neurodegenerative diseases. Importantly, tau pathology spreads in a traumatic brain in a timely manner. In particular, we have recently demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which that cis P-tau is extremely neurotoxic, has a prion nature, and spreads to various brain areas and cerebrospinal fluid (CSF) upon trauma. On the other hand, tau pathology, in particular hyperphosphorylation at Thr231, has been observed upon SCI. Taken these together, we conclude that cis pT231-tau may accumulate and spread in the spinal cord as well as CSF and diffuse tau pathology in the central nervous system (CNS). Moreover, antibody against cis P-tau can target intracellular cis P-tau and protect pathology spreading. Thus, considering cis P-tau as a driver of tau pathology and neurodegeneration upon SCI would open new windows toward understanding the disease development and early biomarkers. Furthermore, it would help us develop effective therapies for SCI patients.

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Funding

The grant of this study was provided by the Neurosciences Research Center of Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran (code of ethics: IR.TBZMED.VCR.REC.1398.067) and Council for Stem Cell Sciences and Technologies, Tehran, Iran (grant number: 11/35721).

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Authors and Affiliations

  1. Neurosciences Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Elnaz Nakhjiri

  2. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark

    Manuchehr S. Vafaee

  3. Department of Neurology, Babol University of Medical Sciences, Babol, Iran

    Seyed Mohammad Massod Hojjati

  4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Parviz Shahabi

  5. Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Koorosh Shahpasand

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  1. Elnaz Nakhjiri
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  2. Manuchehr S. Vafaee
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  3. Seyed Mohammad Massod Hojjati
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  5. Koorosh Shahpasand
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All authors contributed to the study conception and design. Elnaz Nakhjiri expressed the idea of the article and performed the literature search. The first draft of the manuscript was written by Elnaz Nakhjiri, Koorosh Shahpasand, and Parviz Shahabi. All authors edited the manuscript and approved the final manuscript.

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Nakhjiri, E., Vafaee, M.S., Hojjati, S.M.M. et al. Tau Pathology Triggered by Spinal Cord Injury Can Play a Critical Role in the Neurotrauma Development. Mol Neurobiol 57, 4845–4855 (2020). https://doi.org/10.1007/s12035-020-02061-7

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