Effects of taxol on slow and fast axonal transport

Komiya, Yoshiaki; Tashiro, Tomoko

doi:10.1002/cm.970110302

Cited by 32 publications

(18 citation statements)

References 31 publications

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“…Bar: 15 pm. increase in the amount of total detyrosinated tubulin (Gundersen et al, 1987;Bre et al, 1987); and 3) a blockage of intraaxonal transport of tubulin (Komiya and Tashiro, 1988). When cerebellar macroneurons were incubated during 40 min in the presence of 5 pM taxol, Tyr antibody staining decreased to background levels at the proximal part of the axon and completely disappeared all along its length by 2 h of incubation.…”

Section: Discussion the Assembly Of Tyrosinated Microtubules During Amentioning

confidence: 99%

Tyrosinated and detyrosinated microtubules in axonal processes of cerebellar macroneurons grown in culture

Arregui

Busciglio

Cáceres

et al. 1991

J of Neuroscience Research

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We have used the monoclonal antibody YL 1/2 (Tyr) specific for tyrosinated tubulin, and a polyclonal antibody (Glu) specific for detyrosinated tubulin to visualize the distribution of microtubules and microtubule assembly sites during axonal outgrowth. Cerebellar macroneurons growing in culture initially extend several short and thin neurites which have the potential to differentiate either as axons or dendrites (Ferreira and Caceres: Developmental Brain Research 49:205-213, 1989). At the onset of axonal outgrowth the Tyr antibody labels the minor neurites, the axon, and its growth cone, while the Glu antibody only shows immunoreactivity in the axonal shaft. After nocodazole treatment, the Tyr staining disappears, whereas that produced by the Glu antibody remains practically unchanged. When nocodazole was removed, tyrosinated microtubules reappeared first at the tip of the axon, in a more distal region than that occupied by detyrosinated microtubules; another focal site of tyrosinated tubulin incorporation was detected in the cell body. Incorporation of tyrosinated tubulin into growing axons was also studied after taxol treatment. After long incubation periods in the presence of taxol, the Tyr staining disappeared from the axon but remained in the cell body; however, immunoreactivity in this site was negative when the cells were preincubated in the presence of protein synthesis inhibitors. Release from taxol results in the reappearance of Tyr immunoreactivity at the distal end of the axon. Taken collectively, the present results indicate 1) that in cerebellar macroneurons axonal differentiation is accompanied by a temporal and spatial differentiation of microtubules and 2) that there is an active site of tyrosinated tubulin assembly at the tip of axonal processes, and they suggest that the highly tyrosinated domain in this region is a consequence of rapid microtubule turnover and tubulin tyrosine ligase activity.

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Section: Discussion the Assembly Of Tyrosinated Microtubules During Amentioning

confidence: 99%

Tyrosinated and detyrosinated microtubules in axonal processes of cerebellar macroneurons grown in culture

Arregui

Busciglio

Cáceres

et al. 1991

J of Neuroscience Research

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“…While they are thought to primarily exert their cancer-killing effects via disruption of microtubule-mediated cell division, it is less clear how they cause CIPN. Microtubules serve as the track for axonal transport, and taxanes interrupt this in vitro , which may lead to neuropathy 43 (Figure 1). Other data demonstrate damage to mitochondria that may underlie a metabolic axonal failure in CIPN 44, 45 .…”

Section: Drug-specific Clinical Presentations and Neurotoxicity In Cipnmentioning

confidence: 99%

Chemotherapy‐induced peripheral neuropathy: A current review

Staff

Grisold

et al. 2017

Annals of Neurology

612

389

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30–40% of patients treated with neurotoxic chemotherapy will develop CIPN and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents.

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“…Vinca alkaloids act by inhibiting assembly and promoting disassembly of microtubules, whereas taxanes and epothilones hyperstabilize microtubule subunit cross-linking. It is possible (but has not been firmly demonstrated) that disruption of microtubule function in axons following systemic administration of antitubulins inhibits axonal transport [17], thus leading to axonopathy. However, at least in animal models, DRG damage has also been reported.…”

Section: Pathophysiologymentioning

confidence: 99%

Chemotherapy-Induced Neuropathy

Cavaletti

Alberti

Frigeni

et al. 2010

Curr Treat Options Neurol

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Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most severe and unpredictable side effects of modern anticancer treatment. In recent years, a clear understanding of the importance of an integrated approach to CIPN has become evident, and efforts are increasing to better characterize its features and to identify more accurate methods to report and grade its occurrence. The clinically relevant impact of CIPN on cancer patients has been known for a long time, but knowledge of its pathogenetic aspects is still very limited. This incomplete knowledge is one of the major limitations in identifying targets for evidence-based neuroprotective strategies. Nevertheless, several studies have been devoted to the prevention or at least the effective treatment of symptoms secondary to peripheral nerve damage and to the early identification of patients at high risk of developing severe CIPN. Unfortunately, none of these studies has been successful and the optimal management of CIPN patients is still an unmet clinical need. Therefore, the modification of chemotherapy is currently the only available approach to limit the severity of neuropathy in the vast majority of patients. The indications for treatment modification are not universally accepted and they can differ among the various drugs. Generally, treatment modification should be considered as soon as symptoms and signs impair the daily life activities of the patient, but the possibility of a delayed worsening of CIPN after treatment withdrawal ("coasting") should always be considered, and delay of modification decisions should be avoided.

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Effects of taxol on slow and fast axonal transport

Cited by 32 publications

References 31 publications

Tyrosinated and detyrosinated microtubules in axonal processes of cerebellar macroneurons grown in culture

Tyrosinated and detyrosinated microtubules in axonal processes of cerebellar macroneurons grown in culture

Chemotherapy‐induced peripheral neuropathy: A current review

Chemotherapy-Induced Neuropathy

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