Although the discovery of the critical role of alpha-synuclein (alpha-syn) in the pathogenesis of Parkinson's disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of alpha-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other alpha-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, alpha-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of alpha-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting alpha-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.

Calabresi, P., Mechelli, A., Natale, G., Volpicelli-Daley, L., Di Lazzaro, G., Ghiglieri, V., Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction, <<CELL DEATH & DISEASE>>, 2023; 14 (3): N/A-N/A. [doi:10.1038/s41419-023-05672-9] [https://hdl.handle.net/10807/231305]

Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction

Calabresi, Paolo;
2023

Abstract

Although the discovery of the critical role of alpha-synuclein (alpha-syn) in the pathogenesis of Parkinson's disease (PD) is now twenty-five years old, it still represents a milestone in PD research. Abnormal forms of alpha-syn trigger selective and progressive neuronal death through mitochondrial impairment, lysosomal dysfunction, and alteration of calcium homeostasis not only in PD but also in other alpha-syn-related neurodegenerative disorders such as dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, and REM sleep behavior disorder. Furthermore, alpha-syn-dependent early synaptic and plastic alterations and the underlying mechanisms preceding overt neurodegeneration have attracted great interest. In particular, the presence of early inflammation in experimental models and PD patients, occurring before deposition and spreading of alpha-syn, suggests a mechanistic link between inflammation and synaptic dysfunction. The knowledge of these early mechanisms is of seminal importance to support the research on reliable biomarkers to precociously identify the disease and possible disease-modifying therapies targeting alpha-syn. In this review, we will discuss these critical issues, providing a state of the art of the role of this protein in early PD and other synucleinopathies.
2023
Inglese
Calabresi, P., Mechelli, A., Natale, G., Volpicelli-Daley, L., Di Lazzaro, G., Ghiglieri, V., Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction, <<CELL DEATH & DISEASE>>, 2023; 14 (3): N/A-N/A. [doi:10.1038/s41419-023-05672-9] [https://hdl.handle.net/10807/231305]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/231305
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