The role of alpha-synuclein in neurotransmission and synaptic plasticity

Cheng, Fei; Vivacqua, Giorgio; Yu, Shun

doi:10.1016/j.jchemneu.2010.12.001

Cited by 191 publications

(174 citation statements)

References 79 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…α-Synuclein reportedly plays a role in the neuroplasticity [36], and several studies have shown elevated α-synuclein levels in the developing brain and primary cultured cortical neurons from different embryonic stages [41,42]. Our study supports this notion by demonstrating high α-synuclein levels in primary cultured cortical neurons.…”

Section: Melatonin-induced Neuroprotection and Autophagysupporting

confidence: 87%

“…It is possible that arsenics-induced autophagy degrades the engulfed organelles, such as mitochondria, and results in mitochondrial dysfunction [34]. Furthermore, autophagy may sequester functional proteins, such as α-synuclein [35], which reportedly regulates the metabolism of neurotransmitters, synaptic plasticity, and neurite outgrowth [36]. Therefore, investigation of the role of autophagy in melatonin-induced neuroprotection of arsenite-induced neurotoxicity is urged.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Melatonin Ameliorates Arsenite-Induced Neurotoxicity: Involvement of Autophagy and Mitochondria

Teng¹,

Tai²,

Huang

et al. 2015

Mol Neurobiol

View full text Add to dashboard Cite

In the present study, the neuroprotective effect of melatonin on arsenite-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation of melatonin prevented arsenite-induced neuronal cell loss in a concentration-dependent manner. Furthermore, melatonin significantly attenuated arsenite-induced elevation in microtubule-associated protein light chain 3 (LC3)-II levels, a biomarker of autophagy. Our fluorescent staining assay showed that melatonin decreased arsenite-induced elevation of co-localized fluorescent puncta of monodansylcadaverine (a specific marker of autophagic vacuoles) and lysotracker red (a specific marker of lysosomes), indicating that melatonin is capable of inhibiting arsenite-induced autophagy and autolysosome formation. Because 3-methyladenine (an autophagic inhibitor) attenuated the arsenite-reduced α-synuclein levels (a protein essential for the neurite outgrowth and synaptic plasticity), melatonin via inhibiting autophagy attenuated the arsenite-reduced α-synuclein levels. At the same time, melatonin ameliorated the arsenite-induced reduction in growth associated protein 43 (a hallmark protein of neurite outgrowth) and discontinuous neurites of rat primary cultured cortical neurons. In addition, melatonin was found to prevent arsenite-induced decreases in cytochrome c oxidase levels (a biomarker of mitochondrial mass) and elevation in co-localized fluorescent puncta of autolysosomes and cytochrome c oxidase. Moreover, melatonin prevented arsenite-induced reduction in peroxisome proliferator-activated receptor gamma co-activator 1 α, a transcriptional co-activator of mitochondrial biosynthesis. Taken together, melatonin may exert its neuroprotective action via inhibiting arsenite-induced autophagy and enhancing mitochondrial biogenesis and thus restoring α-synuclein levels, neuronal integrity, and mitochondrial mass in rat primary cultured cortical neurons.

show abstract

Section: Melatonin-induced Neuroprotection and Autophagysupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Melatonin Ameliorates Arsenite-Induced Neurotoxicity: Involvement of Autophagy and Mitochondria

Teng¹,

Tai²,

Huang

et al. 2015

Mol Neurobiol

View full text Add to dashboard Cite

show abstract

“…This 140-amino acid protein is abundantly expressed in the presynaptic nerve terminals of dopaminergic neurons (2,3), where it is thought to maintain synaptic vesicles required for neurotransmission (4)(5)(6). Dementia with Lewy bodies (DLB) constitutes a considerable fraction of dementia cases with a prevalence of 15% to 35% (7).…”

Section: Introductionmentioning

confidence: 99%

Pathological Interface Between Oligomeric Alpha-Synuclein and Tau in Synucleinopathies

Sengupta

Guerrero-Muñoz

Castillo-Carranza

et al. 2015

Biological Psychiatry

143

134

View full text Add to dashboard Cite

“…The normal role of α-syn remains unclear, however high concentrations of the protein exist within neuronal presynaptic terminals, indicating potential function(s) in synaptic transmission (Cheng, Vivacqua and Yu, 2011). Multiple specific roles have been proposed for α-syn, including SNARE protein regulation, production of dopamine and regulation of synaptic vesicle recycling (Burre et …”

Section: Alpha Synucleinmentioning

confidence: 99%

Potential Modes of Intercellular Alpha-Synuclein Transmission

Valdinocci

Radford

Siow

et al. 2017

Preprint

View full text Add to dashboard Cite

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson's disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunneling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

show abstract

The role of alpha-synuclein in neurotransmission and synaptic plasticity

Cited by 191 publications

References 79 publications

Melatonin Ameliorates Arsenite-Induced Neurotoxicity: Involvement of Autophagy and Mitochondria

Melatonin Ameliorates Arsenite-Induced Neurotoxicity: Involvement of Autophagy and Mitochondria

Pathological Interface Between Oligomeric Alpha-Synuclein and Tau in Synucleinopathies

Potential Modes of Intercellular Alpha-Synuclein Transmission

Contact Info

Product

Resources

About