Mitochondrial dysfunction has been for long time the primary hypotheses for dopaminergic (DA) neurons death in Parkinson’s disease (PD), but recently Choi and colleagues demonstrated that complex I absence does not protect DA neurons from parkinsonism-inducing toxin as Rotenone and MPP+ (Choi et al., 2008). Morfini and colleagues suggested that the MPP+-induced alteration in fast axonal transport (FAT) is the leading molecular event in dying-back degeneration processes (Morfini et al., 2007), but they didn’t see any appreciable structural alteration of microtubules (MTs), the railways of axonal transport. MTs are a common target of both rotenone (Ren et al., 2005) and MPP+ (Cappelletti et al., 2005), and their relevance in survival of striatal and DA neurons has been recently highlighted (Liang et al., 2008). Furthermore, we recently showed that, in differentiated PC12 cells, alterations of MT organization and stability precede mitochondrial dysfunction and axonal transport impairment (Cartelli et la., 2010). Here we address the question if such temporal chain is present also in vivo, and we show that, in MPTP-treated mice, changes in MT stability anticipate mitochondrial transport impairment and tyrosine hydroxylase (TH) depletion, a marker of ongoing degeneration (Ara et al., 1998).

Microtubule stability is precociously affected in a mouse model of Parkinson's disease / D. Cartelli, F. Casagrande, G. Battaglia, C. Busceti, G. Molinaro, G. Cappelletti. ((Intervento presentato al 5. convegno Meeting on the Molecular Mechanism of Neurodegeneration tenutosi a Milano nel 2011.

Microtubule stability is precociously affected in a mouse model of Parkinson's disease

D. Cartelli;F. Casagrande;G. Cappelletti
2011

Abstract

Mitochondrial dysfunction has been for long time the primary hypotheses for dopaminergic (DA) neurons death in Parkinson’s disease (PD), but recently Choi and colleagues demonstrated that complex I absence does not protect DA neurons from parkinsonism-inducing toxin as Rotenone and MPP+ (Choi et al., 2008). Morfini and colleagues suggested that the MPP+-induced alteration in fast axonal transport (FAT) is the leading molecular event in dying-back degeneration processes (Morfini et al., 2007), but they didn’t see any appreciable structural alteration of microtubules (MTs), the railways of axonal transport. MTs are a common target of both rotenone (Ren et al., 2005) and MPP+ (Cappelletti et al., 2005), and their relevance in survival of striatal and DA neurons has been recently highlighted (Liang et al., 2008). Furthermore, we recently showed that, in differentiated PC12 cells, alterations of MT organization and stability precede mitochondrial dysfunction and axonal transport impairment (Cartelli et la., 2010). Here we address the question if such temporal chain is present also in vivo, and we show that, in MPTP-treated mice, changes in MT stability anticipate mitochondrial transport impairment and tyrosine hydroxylase (TH) depletion, a marker of ongoing degeneration (Ara et al., 1998).
mag-2011
Parkinson’s Disease ; Microtubule Stability ; MPTP
Settore BIO/06 - Anatomia Comparata e Citologia
Microtubule stability is precociously affected in a mouse model of Parkinson's disease / D. Cartelli, F. Casagrande, G. Battaglia, C. Busceti, G. Molinaro, G. Cappelletti. ((Intervento presentato al 5. convegno Meeting on the Molecular Mechanism of Neurodegeneration tenutosi a Milano nel 2011.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/170868
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