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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 and Ciammola, Andrea , et al. (2018) In Neurobiology of Aging 61. p.66-74
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aging, Dopaminergic neurons, Microtubule, Parkin, Parkinson's disease, Tubulin post-translational modifications
in
Neurobiology of Aging
volume
61
pages
66 - 74
publisher
Elsevier
external identifiers
  • scopus:85042875201
  • pmid:29040870
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2017.09.010
language
English
LU publication?
yes
id
76f93191-f17b-4ca9-91f7-af8b5589b429
date added to LUP
2018-03-23 11:32:11
date last changed
2024-05-27 08:58:51
@article{76f93191-f17b-4ca9-91f7-af8b5589b429,
  abstract     = {{<p>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.</p>}},
  author       = {{Cartelli, Daniele and Amadeo, Alida and Calogero, Alessandra Maria and Casagrande, Francesca Vittoria Marialuisa and De Gregorio, Carmelita and Gioria, Mariarosa and Kuzumaki, Naoko and Costa, Ilaria and Sassone, Jenny and Ciammola, Andrea and Hattori, Nobutaka and Okano, Hideyuki and Goldwurm, Stefano and Roybon, Laurent and Pezzoli, Gianni and Cappelletti, Graziella}},
  issn         = {{0197-4580}},
  keywords     = {{Aging; Dopaminergic neurons; Microtubule; Parkin; Parkinson's disease; Tubulin post-translational modifications}},
  language     = {{eng}},
  pages        = {{66--74}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Aging}},
  title        = {{Parkin absence accelerates microtubule aging in dopaminergic neurons}},
  url          = {{http://dx.doi.org/10.1016/j.neurobiolaging.2017.09.010}},
  doi          = {{10.1016/j.neurobiolaging.2017.09.010}},
  volume       = {{61}},
  year         = {{2018}},
}