Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury

Yi, Sheng; Liu, Qianyan; Wang, Xinghui; Qian, Tianmei; Wang, Hongkui; Zha, Guangbin; Yu, Jun; Wang, Pan; Gu, Xiaosong; Chu, Dandan; Li, Shiying

doi:10.1242/jcs.222059

Cited by 38 publications

(21 citation statements)

References 32 publications

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“…Studies exploring the role of tau after injury have also been contradictory. MAPT −/− mice suffer worse functional outcome after sciatic nerve injury [285] and EAE [277], reminiscent of tau regulating physiological myelination (discussed earlier). Several studies, however, report that MAPT −/− mice are resistant to some functional and cognitive deficits after TBI, although this depends on whether the injury was repetitive [45] and whether short-term or long-term outcomes were measured [256].…”

Section: The Effect Of Tau Depends On the Type Of Injury Inducedmentioning

confidence: 94%

“…MAPT −/− mice also show age-dependent degeneration of myelinated fibers, reduced nerve conduction, and progressive hypomyelination [157,237], resulting in motor [157] and nociceptive [237] impairments. Tau knockdown also restricts recovery after sciatic nerve damage, with mice showing defective myelin debris clearance and severely impaired Schwann cell migration and differentiation [285]. Similarly, MAPT −/− mice showed a worse clinical outcome after experimental autoimmune encephalomyelitis (EAE) (a model of demyelinating disease) [277].…”

Section: Tau Is Important For Normal Myelinationmentioning

confidence: 99%

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The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

2020

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Tau and amyloid beta (Aβ) are the prime suspects for driving pathology in Alzheimer’s disease (AD) and, as such, have become the focus of therapeutic development. Recent research, however, shows that these proteins have been highly conserved throughout evolution and may have crucial, physiological roles. Such functions may be lost during AD progression or be unintentionally disrupted by tau- or Aβ-targeting therapies. Tau has been revealed to be more than a simple stabiliser of microtubules, reported to play a role in a range of biological processes including myelination, glucose metabolism, axonal transport, microtubule dynamics, iron homeostasis, neurogenesis, motor function, learning and memory, neuronal excitability, and DNA protection. Aβ is similarly multifunctional, and is proposed to regulate learning and memory, angiogenesis, neurogenesis, repair leaks in the blood–brain barrier, promote recovery from injury, and act as an antimicrobial peptide and tumour suppressor. This review will discuss potential physiological roles of tau and Aβ, highlighting how changes to these functions may contribute to pathology, as well as the implications for therapeutic development. We propose that a balanced consideration of both the physiological and pathological roles of tau and Aβ will be essential for the design of safe and effective therapeutics.

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Section: The Effect Of Tau Depends On the Type Of Injury Inducedmentioning

confidence: 94%

Section: Tau Is Important For Normal Myelinationmentioning

confidence: 99%

The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

2020

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“…Tau is a ubiquitous protein that is primarily expressed in the nervous system [ 7 ], with higher expression levels in neurons than astrocytes, oligodendrocytes, and Schwann cells [ 8 , 9 , 10 ]. In the brain tau, isoform expression is developmentally regulated: in fetal brain is expressed only the shortest isoform 0N3R [ 11 ], whereas the adult human brain shows all the isoforms [ 4 ].…”

Section: The Role Of Tau In Physiological Condition In Axonsmentioning

confidence: 99%

“…Schwann cells provide mechanical and trophic support to peripheral axons and are essential for the maintenance of peripheral nerves’ physiological function. It has been reported that tau is expressed in Schwann cells and is involved in Schwann cells’ mobility and phagocytosis ability; indeed, Yi and colleagues demonstrate that in MAPT -knockout mice, the decrease of tau expression reduced Schwann cell migration and suppressed the ability to clear debris after sciatic nerve injury [ 10 ]. Thus, tau pathology can induce neurotoxicity affecting not only neurons, but also damaging Schwann cells and preventing their trophic and supportive role.…”

Section: Pathological Tau and The Peripheral Nervous Systemmentioning

confidence: 99%

Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core

Vacchi

Kaelin‐Lang

Melli

2020

IJMS

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In neuronal cells, tau is a microtubule-associated protein placed in axons and alpha synuclein is enriched at presynaptic terminals. They display a propensity to form pathologic aggregates, which are considered the underlying cause of Alzheimer’s and Parkinson’s diseases. Their functional impairment induces loss of axonal transport, synaptic and mitochondrial disarray, leading to a “dying back” pattern of degeneration, which starts at the periphery of cells. In addition, pathologic spreading of alpha-synuclein from the peripheral nervous system to the brain through anatomical connectivity has been demonstrated for Parkinson’s disease. Thus, examination of the extent and types of tau and alpha-synuclein in peripheral tissues and their relation to brain neurodegenerative diseases is of relevance since it may provide insights into patterns of protein aggregation and neurodegeneration. Moreover, peripheral nervous tissues are easily accessible in-vivo and can play a relevant role in the early diagnosis of these conditions. Up-to-date investigations of tau species in peripheral tissues are scant and have mainly been restricted to rodents, whereas, more evidence is available on alpha synuclein in peripheral tissues. Here we aim to review the literature on the functional role of tau and alpha synuclein in physiological conditions and disease at the axonal level, their distribution in peripheral tissues, and discuss possible commonalities/diversities as well as their interaction in proteinopathies.

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“…Primary Schwann cells were collected and cultured as previously described [15]. Brie y, cells isolated from neonatal SD rat sciatic nerves were puri ed with anti-Thy1.1 antibody (Sigma, St. Louis, MO, USA) and rabbit complement (Invitrogen, Carlsbad, CA, USA) and then cultured in DMEM (Gibco, Grand Island, NY, USA) containing 10% FBS (Gibco), 1% penicillin and streptomycin (Invitrogen), 2 μM forskolin (Sigma), and 10 ng/ml HRG (R&D Systems Inc., Minneapolis, MN, USA).…”

Section: Schwann Cell Culture and Treatmentmentioning

confidence: 99%

Betacellulin Regulates Peripheral Nerve Regeneration by Affecting Schwann Cell Migration and Axon Elongation

Wang

Zhang

et al. 2021

Preprint

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Background Growth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve injury and regeneration. Our previous sequencing analysis found that betacellulin (Btc), an epidermal growth factor protein family member, showed elevated mRNA expressions in the nerve segment after rat peripheral nerve injury, implying the potential involvement of Btc during peripheral nerve repair. Methods Expression of Btc was examined in Schwann cells. The role of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or exposed cultured cells with Btc recombinant protein, respectively. The biological functions of Schwann cell-secreted Btc on neurons were also determined. Moreover, the in vivo effect of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated.Results Immunostaining images and ELISA readings showed Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that siRNA against Btc impeded Schwann cell migration while exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells might influence neuron behavior and affect axon length. In vivo evidence showed that Btc enhanced axonal regrowth and nerve regeneration after both rat sciatic nerve crush injury and transection injury. Conclusion Our findings demonstrated Btc-mediated Schwann cell-axon interactions, revealed the essential roles of Btc on Schwann cell migration and axon elongation, and implied the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.

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Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury

Cited by 38 publications

References 32 publications

The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics

Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core

Betacellulin Regulates Peripheral Nerve Regeneration by Affecting Schwann Cell Migration and Axon Elongation

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