What is the biological significance of the brain-specific tubulin-polymerization promoting protein (TPPP/p25)?

Ovádi, Judit; Orosz, Ferenc; Lebotzky, Attila

doi:10.1080/15216540500381101

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Recent in vitro and in vivo data have shown that the primary target of TPPP/p25 is the tubulin/microtubule, and its physiological function is likely the stabilization of the microtubular system, which is fulfilled via its bundling activity [20]. The interaction of TPPP/p25 with α‐synuclein, a marker of PD and other synucleinopathies, was demonstrated as well [21].…”

Section: Resultsmentioning

confidence: 97%

Interaction of TPPP/p25 protein with glyceraldehyde‐3‐phosphate dehydrogenase and their co‐localization in Lewy bodies

et al. 2006

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TPPP/p25, a flexible unstructured protein, binds to tubulin and induces aberrant microtubule assemblies. We identified hereby glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a new interacting partner of TPPP/p25. The immunoprecipitation and affinity chromatographic experiments with bovine brain cell-free extract revealed that the interaction was salt and NAD + sensitive while ELISA showed resistant and firm association of the two isolated proteins. In transfected HeLa cells at low expression level of EGFP-TPPP/p25, while the green fusion protein aligned at the microtubular network, GAPDH distributed uniformly in the cytosol. However, at high expression level, GAPDH co-localized with TPPP/p25 in the aggresome-like aggregate. Immunohistochemistry showed enrichment of TPPP/ p25 and GAPDH within the a-synuclein positive Lewy body.

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Section: Resultsmentioning

confidence: 97%

Interaction of TPPP/p25 protein with glyceraldehyde‐3‐phosphate dehydrogenase and their co‐localization in Lewy bodies

et al. 2006

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“…Thus, its suppression may allow MT-defective cells to bypass the CHFR-checkpoint and promote genomic instability. The tubulin polymerization promoting protein (TPPP), whose mRNA expression was repressed (>4 fold, see Tables S2C & S2D ) by rotenone, is also involved in MT stabilization [65]. The downregulated CAV1 gene (>5 fold, see Tables S2D ) encodes for another upregulator of MT polymerization [66].…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis of a Rotenone Model of Parkinsonism Reveals Complex I-Tied and -Untied Toxicity Mechanisms Common to Neurodegenerative Diseases

Cabeza-Arvelaiz

Schiestl

2012

PLoS ONE

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The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.

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“…In the OLN-93 model of MSA generated by Kragh and colleagues [ 48 ], MSA-like glial degeneration was induced specifically by co-expression of α-synuclein with p25α, an oligodendrocyte protein involved in basic microtubule assembly and myelination [ 72 , 73 ]. Varying the levels of α-synuclein expression further showed that there was a low threshold for cytotoxicity when p25α was present.…”

Section: Reviewmentioning

confidence: 99%

Animal modeling an oligodendrogliopathy – multiple system atrophy

Bleasel

Halliday

Kim

2016

acta neuropathol commun

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Multiple system atrophy (MSA) is a rare, yet rapidly-progressive neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. The definitive neuropathology differentiating MSA from Lewy body diseases is the presence of α-synuclein aggregates in oligodendrocytes (called glial cytoplasmic inclusion or GCI) rather than the fibrillar aggregates in neurons (called Lewy bodies). This makes the pathological pathway(s) in MSA unique in that oligodendrocytes are involved rather than predominantly neurons, as is most other neurodegenerative disorders. MSA is therefore regarded as an oligodendrogliopathy. The etiology of MSA is unknown. No definitive risk factors have been identified, although α-synuclein and other genes have been variably linked to MSA risk. Utilization of postmortem brain tissues has greatly advanced our understanding of GCI pathology and the subsequent neurodegeneration. However, extrapolating the early pathogenesis of MSA from such resource has been difficult and limiting. In recent years, cell and animal models developed for MSA have been instrumental in delineating unique MSA pathological pathways, as well as aiding in clinical phenotyping. The purpose of this review is to bring together and discuss various animal models that have been developed for MSA and how they have advanced our understanding of MSA pathogenesis, particularly the dynamics of α-synuclein aggregation. This review will also discuss how animal models have been used to explore potential therapeutic avenues for MSA, and future directions of MSA modeling.

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What is the biological significance of the brain-specific tubulin-polymerization promoting protein (TPPP/p25)?

Cited by 5 publications

References 25 publications

Interaction of TPPP/p25 protein with glyceraldehyde‐3‐phosphate dehydrogenase and their co‐localization in Lewy bodies

Interaction of TPPP/p25 protein with glyceraldehyde‐3‐phosphate dehydrogenase and their co‐localization in Lewy bodies

Transcriptome Analysis of a Rotenone Model of Parkinsonism Reveals Complex I-Tied and -Untied Toxicity Mechanisms Common to Neurodegenerative Diseases

Animal modeling an oligodendrogliopathy – multiple system atrophy

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