Parkin absence accelerates microtubule aging in dopaminergic neurons

Daniele Cartelli, Alida Amadeo, Alessandra Maria Calogero, Francesca Vittoria Marialuisa Casagrande, Carmelita De Gregorio, Mariarosa Gioria, Naoko Kuzumaki, Ilaria Costa, Jenny Sassone, Andrea Ciammola, Nobutaka Hattori, Hideyuki Okano, Stefano Goldwurm, Laurent Roybon, Gianni Pezzoli, Graziella Cappelletti

研究成果: Article

6 引用 (Scopus)

抄録

Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport. Moreover, in-cell experiments confirmed that loss of parkin affects mitochondria mobility and showed that this defect depends on MT system as it is rescued by paclitaxel, a well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in patients' induced pluripotent stem cell–derived midbrain neurons, we observed that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we suggest that parkin acts as a regulator of MT system during neuronal aging, and we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis of Parkinson's disease.

元の言語English
ページ(範囲)66-74
ページ数9
ジャーナルNeurobiology of Aging
61
DOI
出版物ステータスPublished - 2018 1 1

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Dopaminergic Neurons
Microtubules
Mitochondria
Knockout Mice
Parkinson Disease
Corpus Striatum
PC12 Cells
Substantia Nigra
Acetylation
Mesencephalon
Paclitaxel
Homeostasis
Neurons
Mutation
Genes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

これを引用

Cartelli, D., Amadeo, A., Calogero, A. M., Casagrande, F. V. M., De Gregorio, C., Gioria, M., ... Cappelletti, G. (2018). Parkin absence accelerates microtubule aging in dopaminergic neurons. Neurobiology of Aging, 61, 66-74. https://doi.org/10.1016/j.neurobiolaging.2017.09.010

Parkin absence accelerates microtubule aging in dopaminergic neurons. / Cartelli, Daniele; Amadeo, Alida; Calogero, Alessandra Maria; Casagrande, Francesca Vittoria Marialuisa; De Gregorio, Carmelita; Gioria, Mariarosa; Kuzumaki, Naoko; Costa, Ilaria; Sassone, Jenny; Ciammola, Andrea; Hattori, Nobutaka; Okano, Hideyuki; Goldwurm, Stefano; Roybon, Laurent; Pezzoli, Gianni; Cappelletti, Graziella.

:: Neurobiology of Aging, 巻 61, 01.01.2018, p. 66-74.

研究成果: Article

Cartelli, D, Amadeo, A, Calogero, AM, Casagrande, FVM, De Gregorio, C, Gioria, M, Kuzumaki, N, Costa, I, Sassone, J, Ciammola, A, Hattori, N, Okano, H, Goldwurm, S, Roybon, L, Pezzoli, G & Cappelletti, G 2018, 'Parkin absence accelerates microtubule aging in dopaminergic neurons', Neurobiology of Aging, 巻. 61, pp. 66-74. https://doi.org/10.1016/j.neurobiolaging.2017.09.010
Cartelli D, Amadeo A, Calogero AM, Casagrande FVM, De Gregorio C, Gioria M その他. Parkin absence accelerates microtubule aging in dopaminergic neurons. Neurobiology of Aging. 2018 1 1;61:66-74. https://doi.org/10.1016/j.neurobiolaging.2017.09.010
Cartelli, Daniele ; Amadeo, Alida ; Calogero, Alessandra Maria ; Casagrande, Francesca Vittoria Marialuisa ; De Gregorio, Carmelita ; Gioria, Mariarosa ; Kuzumaki, Naoko ; Costa, Ilaria ; Sassone, Jenny ; Ciammola, Andrea ; Hattori, Nobutaka ; Okano, Hideyuki ; Goldwurm, Stefano ; Roybon, Laurent ; Pezzoli, Gianni ; Cappelletti, Graziella. / Parkin absence accelerates microtubule aging in dopaminergic neurons. :: Neurobiology of Aging. 2018 ; 巻 61. pp. 66-74.
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abstract = "Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport. Moreover, in-cell experiments confirmed that loss of parkin affects mitochondria mobility and showed that this defect depends on MT system as it is rescued by paclitaxel, a well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in patients' induced pluripotent stem cell–derived midbrain neurons, we observed that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we suggest that parkin acts as a regulator of MT system during neuronal aging, and we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis of Parkinson's disease.",
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AU - De Gregorio, Carmelita

AU - Gioria, Mariarosa

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