The appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and both in vivo and in vitro models support the hypothesis that nigrostriatal synapses may indeed be affected at the earliest stages of the neurodegenerative process. The mechanisms leading to either structural or functional synaptic dysfunction are starting to be elucidated and include dysregulation of axonal transport, impairment of the exocytosis and endocytosis machinery, altered intracellular trafficking, and loss of corticostriatal synaptic plasticity. The aim of this review is to try to integrate different lines of evidence from both pathogenic and genetic animal models that, to different extents, suggest that early synaptic impairment may represent the key event in PD pathogenesis. Understanding the molecular and cellular events underlying such synaptopathy is a fundamental step toward developing specific biomarkers of early dopaminergic dysfunction and, more importantly, designing novel therapies targeting the synaptic apparatus of selective, vulnerable synapses. © 2016 International Parkinson and Movement Disorder Society.

Schirinzi, T., Madeo, G., Martella, G., Maltese, M., Picconi, B., Calabresi, P., et al. (2016). Early synaptic dysfunction in Parkinson's disease: Insights from animal models. MOVEMENT DISORDERS, 31(6), 802-813 [10.1002/mds.26620].

Early synaptic dysfunction in Parkinson's disease: Insights from animal models

SCHIRINZI, TOMMASO;MADEO, GRAZIELLA;MARTELLA, GIUSEPPINA;PICCONI, BARBARA;CALABRESI, PAOLO;PISANI, ANTONIO
2016-01-01

Abstract

The appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and both in vivo and in vitro models support the hypothesis that nigrostriatal synapses may indeed be affected at the earliest stages of the neurodegenerative process. The mechanisms leading to either structural or functional synaptic dysfunction are starting to be elucidated and include dysregulation of axonal transport, impairment of the exocytosis and endocytosis machinery, altered intracellular trafficking, and loss of corticostriatal synaptic plasticity. The aim of this review is to try to integrate different lines of evidence from both pathogenic and genetic animal models that, to different extents, suggest that early synaptic impairment may represent the key event in PD pathogenesis. Understanding the molecular and cellular events underlying such synaptopathy is a fundamental step toward developing specific biomarkers of early dopaminergic dysfunction and, more importantly, designing novel therapies targeting the synaptic apparatus of selective, vulnerable synapses. © 2016 International Parkinson and Movement Disorder Society.
2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Parkinson's disease; presymptomatic stage; substantia nigra; synaptopathy
Schirinzi, T., Madeo, G., Martella, G., Maltese, M., Picconi, B., Calabresi, P., et al. (2016). Early synaptic dysfunction in Parkinson's disease: Insights from animal models. MOVEMENT DISORDERS, 31(6), 802-813 [10.1002/mds.26620].
Schirinzi, T; Madeo, G; Martella, G; Maltese, M; Picconi, B; Calabresi, P; Pisani, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/168936
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