A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo

Somayaji, Mahalakshmi; Cataldi, Stefano; Choi, Se Joon; Edwards, Robert H.; Mosharov, Eugene V.; Sulzer, David

doi:10.1073/pnas.2013652117

Cited by 46 publications

(51 citation statements)

References 63 publications

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“…The current investigation showed that SADS-CoV was only detected in Guangdong, but not in other areas; previous studies found it to exist in Fujian (Li et al 2018 ), so it is necessary to strengthen the monitoring of SADS-CoV to prevent it from spreading to other areas. Previous studies have shown that the coronavirus has extensive in vitro host tropism and can infect a variety of cell lines (Edwards et al 2020 ; Luo et al 2020 ; Yang et al 2020 , 2019 ). At the same time, mixed infections may lead to recombinations between viruses and changes in the virulence of the virus (Akimkin et al 2016 ; Ding et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Use of dual priming oligonucleotide system-based multiplex RT-PCR assay to detect five diarrhea viruses in pig herds in South China

Niu

Zhou

et al. 2021

AMB Expr

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In this study, a specific and simple method based on the dual priming oligonucleotide (DPO) system was developed to simultaneously detect transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine rotavirus A (PRV-A), porcine delta coronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), associated with the major enteric RNA viruses in pigs. The DPO system-based multiplex RT-PCR method simplified the primer design and did not require optimization of the annealing temperature. Specificity analysis revealed that the method could specifically detect TGEV, PEDV, PRV-A, PDCoV, and SADS-CoV without any cross-amplification of other circulating swine viruses. The limit of detection of the method was as low as 103–104 copies/μL plasmid of each virus. The method also had good repeatability, and obvious results were seen in three repeat experiments with an interval of 45 days. This optimized multiplex RT-PCR method was used to evaluate 181 clinical swine samples that were collected from four provinces of China between September 2016 and August 2018. The results showed that the positive detection rates of PEDV, PDCoV, SADS-CoV, PRV-A, and TGEV were 30.94% (56/181), 17.67% (32/181), 11.6% (21/181), 9.39% (17/181), and 0.55% (1/181), respectively. Mixed infection of two or more viruses was also common. The DPO system-based multiplex RT-PCR could be a useful tool for detecting enteric virus infections. This method has the advantages of easy operation, low cost, high detection efficiency, and short running time for early diagnosis in clinical cases.

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Section: Discussionmentioning

confidence: 99%

Use of dual priming oligonucleotide system-based multiplex RT-PCR assay to detect five diarrhea viruses in pig herds in South China

Niu

Zhou

et al. 2021

AMB Expr

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“…Considering its degree of conservation among vertebrates, loss of all three synuclein genes has remarkably little effect on the survival or function of mice 37 , 38 . However, it is very clear that overexpression of aSyn (or bSYN) inhibits synaptic vesicle exocytosis 39 , 40 and modulates dopamine release depending on specific patterns of neuronal activity 41 . This occurs in the absence of overt toxicity or aggregation but may, nonetheless, involve some form of injury because loss of the endogenous proteins does not substantially alter neurotransmitter release.…”

Section: Function and Localization Of Alpha-synucleinmentioning

confidence: 99%

Alpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease

Oliveira

Gasser

Edwards

et al. 2021

npj Parkinsons Dis.

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With the advent of the genetic era in Parkinson’s disease (PD) research in 1997, α-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an economic impact of $51.9 billion in the US alone. Since the initial association with PD, hundreds of researchers have contributed to elucidating the functions of α-synuclein in normal and pathological states, and these remain critical areas for continued research. With this position paper the authors strive to achieve two goals: first, to succinctly summarize the critical features that define α-synuclein’s varied roles, as they are known today; and second, to identify the most pressing knowledge gaps and delineate a multipronged strategy for future research with the goal of enabling therapies to stop or slow disease progression in PD.

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“…However, due to its presence in synapses, ASN is suggested to be connected with synaptic vesicle regulation and neurotransmission [17,18]. ASN is postulated to be an essential regulator of dopamine (DA) signaling [19]. Moreover, ASN has been reported to modulate axon outgrowth, and was suggested to be involved in compensation mechanisms, implicating corticostriatal glutamatergic plasticity, which occur in early PD [20].…”

Section: Asn and Its Role In Physiology And Pd Pathogenesis 21 Physiological Function Of Asnmentioning

confidence: 99%

Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson’s Disease

Motyl

Strosznajder

Wencel

et al. 2021

IJMS

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Molecular studies have provided increasing evidence that Parkinson’s disease (PD) is a protein conformational disease, where the spread of alpha-synuclein (ASN) pathology along the neuraxis correlates with clinical disease outcome. Pathogenic forms of ASN evoke oxidative stress (OS), neuroinflammation, and protein alterations in neighboring cells, thereby intensifying ASN toxicity, neurodegeneration, and neuronal death. A number of evidence suggest that homeostasis between bioactive sphingolipids with opposing function—e.g., sphingosine-1-phosphate (S1P) and ceramide—is essential in pro-survival signaling and cell defense against OS. In contrast, imbalance of the “sphingolipid biostat” favoring pro-oxidative/pro-apoptotic ceramide-mediated changes have been indicated in PD and other neurodegenerative disorders. Therefore, we focused on the role of sphingolipid alterations in ASN burden, as well as in a vast range of its neurotoxic effects. Sphingolipid homeostasis is principally directed by sphingosine kinases (SphKs), which synthesize S1P—a potent lipid mediator regulating cell fate and inflammatory response—making SphK/S1P signaling an essential pharmacological target. A growing number of studies have shown that S1P receptor modulators, and agonists are promising protectants in several neurological diseases. This review demonstrates the relationship between ASN toxicity and alteration of SphK-dependent S1P signaling in OS, neuroinflammation, and neuronal death. Moreover, we discuss the S1P receptor-mediated pathways as a novel promising therapeutic approach in PD.

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A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo

Cited by 46 publications

References 63 publications

Use of dual priming oligonucleotide system-based multiplex RT-PCR assay to detect five diarrhea viruses in pig herds in South China

Use of dual priming oligonucleotide system-based multiplex RT-PCR assay to detect five diarrhea viruses in pig herds in South China

Alpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease

Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson’s Disease

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