Cytosolic aspartate aminotransferase, a direct binding protein of kamikihito, regulates axon growth

Watari, Hidetoshi; Shimada, Yutaka; Tohda, Chihiro

doi:10.1002/tkm2.1037

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…59) Our study found that KKT treatment reversed Aβ-induced tau phosphorylation via protein phosphatase 2A (PP2A). 60) However, inactivation of PP2A by Aβ and activation of PP2A by KKT in neurons was not robust. This suggested that other main signaling pathways might work in KKT-mediated axon regeneration.…”

Section: Usefulness Of Darts Methods For Iden-tifying Unknown Signalingmentioning

confidence: 98%

New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction

Tohda

2016

Biological & Pharmaceutical Bulletin

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Alzheimer's disease (AD) is a recognized incurable neurodegenerative disorder. Clinically prescribed medicines for AD are expected to bring about only slight symptomatic improvement or a delay of its progression. Another strategy, amyloid β (Aβ) lowing agents, has not been successful at memory improvement. We have hypothesized that an improvement in cognitive function requires the construction of neuronal networks, including neurite regeneration and synapse formation; therefore, we have been exploring candidates for radical anti-AD drugs that can restore Aβ-induced neurite atrophy and memory impairment. Our studies found several promising drug candidates that may improve memory dysfunction in AD model mice. The main activity of these drugs is the restoration of damaged axons. Focusing on candidates based on the recovery of neurite atrophy in vitro certainly leads to positive effects on memory improvement also in vivo. This suggests that neuronal network reconstruction may importantly relate to functional recovery in the brain. When identifying the signaling mechanisms of exogenous compounds like natural medicine-derived constituents, molecules directly activated by the compound are hard to be identified. However, the drug affinity responsive target stability (DARTS) analysis may pave the way to an approach to determine the initial molecule of the signaling pathway. Exploring new drug candidates and clarifying their signaling pathways directly relating to neuronal network reconstruction may provide promising therapeutic strategies with which to overcome AD.

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Section: Usefulness Of Darts Methods For Iden-tifying Unknown Signalingmentioning

confidence: 98%

New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction

Tohda

2016

Biological & Pharmaceutical Bulletin

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“…We found that kamikihito also induced axonal growth in the Aβ-treated neuron culture and induced improvement in degenerated axons and memory in 5XFAD mice [ 39 , 98 ]. Using the DARTS method, cytosolic aspartate aminotransferase (cAST) was identified as the direct binding protein candidate of kamikihito [ 99 ]. Knock-down and pharmacological inhibition of cAST diminished the axonal growth activity of kamikihito.…”

Section: Recovery From Aβ-induced Axonal Degenerationmentioning

confidence: 99%

Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer’s Disease

Kuboyama

Yang

Tohda

2020

IJMS

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In Alzheimer’s disease (AD), amyloid β (Aβ) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce Aβ have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, Aβ deposition occurred before the onset of AD. Once neuronal networks were disrupted by Aβ, they could hardly be recovered. Therefore, we speculated that only removal of Aβ was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of Aβ-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from Aβ-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.

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Cytosolic aspartate aminotransferase, a direct binding protein of kamikihito, regulates axon growth

Cited by 2 publications

References 13 publications

New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction

New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction

Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer’s Disease

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