From α-synuclein to synaptic dysfunctions: New insights into the pathophysiology of Parkinson's disease

Bellucci, Arianna; Zaltieri, Michela; Navarria, Laura; Grigoletto, Jéssica; Missale, Cristina; Spano, PierFranco

doi:10.1016/j.brainres.2012.04.014

Cited by 94 publications

(95 citation statements)

References 233 publications

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“…α-synuclein (α-syn, also known as SNCA) deposition in Lewy bodies (LB), that with nigrostriatal dopamine neuron loss are the key neuropathological features of Parkinson's disease, is crucial for the normal synaptic function of these cells Bellucci et al, 2012). For instance, α-syn acts as a negative regulator of nigrostriatal dopaminergic neuron function (Abeliovich et al, 2000;Larsen et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

Zaltieri

Grigoletto

Longhena

et al. 2015

Journal of Cell Science

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106

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The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain α-synuclein (α-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that α-syn interacts with and modulates synapsin III. The absence of α-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In α-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in α-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of α-syn and synapsin III in the regulation of dopamine neuron synaptic function.

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Section: Introductionmentioning

confidence: 99%

α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

Zaltieri

Grigoletto

Longhena

et al. 2015

Journal of Cell Science

Self Cite

106

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“…13 Some authors have suggested that impairment of axonal transport causes accumulation of axonally transported substances followed by cortical Lewy body formation. 14,15 In other words, alterations…”

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confidence: 99%

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease

Shin

Lee³

et al. 2015

American Journal of Neuroradiology

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BACKGROUND AND PURPOSE:The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment.

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“…Aggregation of a-synuclein can obstruct normal cellular transport, leading to impaired intracellular trafficking and/or trapping of cellular organelles in inappropriate locations, this resulting in synaptic and cell dysfunctions (Cookson, 2005;Bartels et al, 2011;Bellucci et al, 2012;Games et al, 2013;Hunn et al, 2015).…”

Section: How This Key Event Workmentioning

confidence: 99%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP's informed Integrated Approach for Testing and Assessment (IATA).

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From α-synuclein to synaptic dysfunctions: New insights into the pathophysiology of Parkinson's disease

Cited by 94 publications

References 233 publications

α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

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