Levels of kinesin light chain and dynein intermediate chain are reduced in the frontal cortex in Alzheimer’s disease: implications for axoplasmic transport

Morel, Marie Hélène; Héraud, Céline; Nicaise, Charles; Suain, Valérie; Brion, Jean Pierre

doi:10.1007/s00401-011-0901-4

Cited by 38 publications

(28 citation statements)

References 51 publications

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“…Tau reduces the number of motors that are engaged with cargoes and thereby interferes with axonal transport of cargoes [491]. Protein levels of both the kinesin motor-mediated axonal transport machinery and of the dynein-mediated retrograde transport machinery are reduced in AD [346]. Such reductions, especially of kinesin light chain and dynein intermediate chain compromise the capacity of these motor proteins.…”

Section: Tau-mediated Neurodegenerationmentioning

confidence: 99%

Roles of tau protein in health and disease

2017

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Tau is well established as a microtubule-associated protein in neurons. However, under pathological conditions, aberrant assembly of tau into insoluble aggregates is accompanied by synaptic dysfunction and neural cell death in a range of neurodegenerative disorders, collectively referred to as tauopathies. Recent advances in our understanding of the multiple functions and different locations of tau inside and outside neurons have revealed novel insights into its importance in a diverse range of molecular pathways including cell signalling, synaptic plasticity, and regulation of genomic stability. The present review describes the physiological and pathophysiological properties of tau and how these relate to its distribution and functions in neurons. We highlight the post-translational modifications of tau, which are pivotal in defining and modulating tau localisation and its roles in health and disease. We include discussion of other pathologically relevant changes in tau, including mutation and aggregation, and how these aspects impinge on the propensity of tau to propagate, and potentially drive neuronal loss, in diseased brain. Finally, we describe the cascade of pathological events that may be driven by tau dysfunction, including impaired axonal transport, alterations in synapse and mitochondrial function, activation of the unfolded protein response and defective protein degradation. It is important to fully understand the range of neuronal functions attributed to tau, since this will provide vital information on its involvement in the development and pathogenesis of disease. Such knowledge will enable determination of which critical molecular pathways should be targeted by potential therapeutic agents developed for the treatment of tauopathies.

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Section: Tau-mediated Neurodegenerationmentioning

confidence: 99%

Roles of tau protein in health and disease

2017

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“…Protein levels of both the kinesin motor-mediated axonal transport machinery and of the dynein-mediated retrograde transport machinery are reduced in Alzheimer’s disease [29]. Kinesin motors enable long-range transport.…”

Section: Mechanisms Of Tau Neurotoxicitymentioning

confidence: 99%

Connecting the dots between tau dysfunction and neurodegeneration

Frost

Götz

Feany

2015

Trends in Cell Biology

107

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Tauopathies are devastating and ultimately fatal neurodegenerative diseases, which are histopathologically defined by insoluble filamentous deposits of abnormally phosphorylated tau protein within neurons and glia. Identifying the causes of abnormal tau phosphorylation and subsequent aggregation has been the focus of much research, and is currently a major target for the development of therapeutic interventions for tauopathies, including Alzheimer’s disease. Recently much has been learned about the sequence of events that lead from tau dysfunction to neuronal death. This review focuses on the cascade of events that are catalyzed by pathological tau, and highlights current and potential therapeutic strategies to target this pathway.

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“…Therefore, mitochondrial transport is complicated and HUMMR might only play a tiny role or have no function in mitochondrial transport in APP/PS1 transgenic mice. Other proteins such as dynein and kinesin may play an important role in mitochondrial transport based on human studies on patients with AD [28]. However, other mechanisms also play an important role in mitochondrial dysfunction, such as oxidative damage [29] and mitochondrial respiratory chain dysfunction [30].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease

Zou

Yu²,

et al. 2013

Dement Geriatr Cogn Disord

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Background/Aims: It has been demonstrated that mitochondrial dysfunction is associated with Alzheimer's disease (AD); meanwhile, hypoxia-up-regulated mitochondrial movement regulator (HUMMR) plays an important role in regulating mitochondrial function. The present study aimed to confirm the association between HUMMR and mitochondrial function in AD. Methods: We detected the expression of HUMMR at transcriptional and translational levels in APP/PS1 double transgenic mice using real-time quantitative RT-PCR and Western blotting. Age- and gender-matched wild-type (WT) littermates were used as controls. Mitochondrial morphology was observed in the hippocampus and cortex of APP/PS1 double transgenic mice using transmission electron microscopy. Results: Damage to mitochondrial morphology in the hippocampus and cortex of APP/PS1 double transgenic mice was found, including swelling and cavitations. Our analysis showed no statistical differences in the expression of HUMMR between APP/PS1 double transgenic mice and WT littermates (p > 0.05). These results showed that there was no association between HUMMR and mitochondrial dysfunction in APP/PS1 transgenic mice. Conclusion: These results indicate that HUMMR does not play a key role in mitochondrial dysfunction in the APP/PS1 double transgenic AD mouse.

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Levels of kinesin light chain and dynein intermediate chain are reduced in the frontal cortex in Alzheimer’s disease: implications for axoplasmic transport

Cited by 38 publications

References 51 publications

Roles of tau protein in health and disease

Roles of tau protein in health and disease

Connecting the dots between tau dysfunction and neurodegeneration

Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease

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