Alpha-synuclein synaptic pathology and its implications in the development of novel therapeutic approaches to cure Parkinson's disease

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

doi:10.1016/j.brainres.2011.11.031

Cited by 38 publications

(29 citation statements)

References 214 publications

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“…In contrast to fibrillar α-syn, oligomeric aggregates are most likely located in axons (FIG. 1B) and presynaptic terminals where they might damage synapses and dendrites 25, 26, 28, 80-82 …”

Section: α-Synuclein and Diseasementioning

confidence: 99%

The many faces of α-synuclein: from structure and toxicity to therapeutic target

et al. 2012

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Disorders characterized by α-synuclein (α-syn) accumulation, Lewy body formation and parkinsonism (and in some cases dementia) are collectively known as Lewy body diseases. The molecular mechanism(s) through which α-syn abnormally accumulates and contributes to neurodegeneration in these disorders remains unknown. Here, we provide an overview of current knowledge and prevailing hypotheses regarding the conformational, oligomerization and aggregation states of α-syn and their role in regulating α-syn function in health and disease. Understanding the nature of the various α-syn structures, how they are formed, and their relative contributions to α-syn-mediated toxicity may inform future studies aiming to develop therapeutic prevention and intervention.

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Section: α-Synuclein and Diseasementioning

confidence: 99%

The many faces of α-synuclein: from structure and toxicity to therapeutic target

et al. 2012

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“…Snca is a natively unfolded protein which plays a central role in the control of dopaminergic neuronal functions and which is thought to be critically implicated in PD pathophysiology. Defects in Snca have been implicated in the pathogenesis of PD [108]. PD is characterized by a progressive loss of dopaminergic neurons of the nigrostriatal system and by the presence of Lewy bodies, proteinaceous inclusions mainly composed of filamentous Snca aggregates.…”

Section: Discussionmentioning

confidence: 99%

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

Manavalan

Mishra²,

Sze³

et al. 2013

Neurosignals

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p60 transcription regulator protein (p60TRP) facilitates the processing of the amyloid precursor protein towards the non-amyloidogenic pathway by inhibiting the β-secretase action. This protein was initially identified to be downregulated in the temporal lobe of brains from Alzheimer's disease patients. p60TRP is one of the G-protein-coupled receptor (GPCR)-associated proteins which directly influences the signalling capacity of GPCRs. In the present study, we investigated the brain-region-specific proteome profile of transgenic p60TRP mice to gain an insight into the molecular events mediated by the long-term effect of neuronal p60TRP overexpression on brain proteome changes and its potential implication for neuronal functions in the central nervous system. Using a proteomics research approach based on isobaric tags for relative and absolute quantitation, we identified 2,025 proteins, whereby 1,735 proteins were quantified, out of which 56 were found to be significantly altered in the cortex and/or hippocampus of neuronal transgenic neuronal p60TRP mice. Our data suggests that in vivo overexpression of neuronal p60TRP significantly affects cognitive and neuroprotective capacities.

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“…PQ, 1-methyl-4-phenylpyridine (MPP + ), and rotenone, but not maneb are known to induce synucleinopathy and tauopathy in striata of mice [57][58][59][60][61]. In addition to abnormal expression of -synuclein, alterations in protein degradation pathways have been implicated in PD by both genetic and pathological studies in PD patients as well as experimental studies in disease models [50,51,62].…”

Section: Autophagymentioning

confidence: 98%

“…a-Synuclein is a natively unfolded protein that plays a central role in the control of synaptic membrane processes and biogenesis, but when it becomes misfolded, aggregates, and accumulates in neuronal inclusion bodies, the Lewy bodies [51]. PQ markedly induces the in vitro conformational changes in a-synuclein, and accelerates the rate of aggregation of a-synuclein [52,53].…”

Section: Autophagymentioning

confidence: 99%

Paraquat: Molecular Mechanisms of Neurotoxicity and its Relation with Autophagy

Baltazar

Dinis-Oliveira

Bastos

et al. 2015

Current Topics in Neurotoxicity

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Paraquat (1,1´-dimethyl-4,4´-bipyridilium dichloride; PQ) is an effective and widely used herbicide in Asiatic and American countries with a claimed safety record when appropriately applied to eliminate weeds. However, over the last decades a growing body of epidemiologic evidence has been linking longterm/low-dose PQ exposure to the development of Parkinson's disease (PD). PQ is well known for its ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillation and neuronal cell loss. More recently, more attention has been given to the role of autophagy in several major neurodegenerative diseases and the influence of environmental toxins in this pathway. This chapter provides an overview of the main mechanisms of neurotoxicity of PQ with an emphasis in the autophagic process and its possible relationship to PD.Keywords Paraquat · Oxidative stress · Autophagy · Neurotoxicity · Neurodegenerative diseases 160 M. T. Baltazar et al.

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Alpha-synuclein synaptic pathology and its implications in the development of novel therapeutic approaches to cure Parkinson's disease

Cited by 38 publications

References 214 publications

The many faces of α-synuclein: from structure and toxicity to therapeutic target

The many faces of α-synuclein: from structure and toxicity to therapeutic target

Brain-Site-Specific Proteome Changes Induced by Neuronal P60TRP Expression

Paraquat: Molecular Mechanisms of Neurotoxicity and its Relation with Autophagy

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