Extensive nuclear localization of α-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody

Yu, Shun; Li, X.; Liu, G.; Han, Junyan; Zhang, C.; Li, Y.; Xu, Shangcheng; Liu, C.; Gao, Yubin; Yang, Hui; Uéda, Kenji; Chan, Piu

doi:10.1016/j.neuroscience.2006.12.028

Cited by 169 publications

(150 citation statements)

References 54 publications

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“…In addition, though, the present results for the first time indicate that virtually all of these efferent axonal projections are positive for alpha-synuclein. The finding that the protein is ubiquitous in vagal efferent terminals in the gut is consistent with the apparently extensive--and perhaps universal--expression of alpha-synuclein observed in the somata of dmnX neurons (Li et al, 2002;Bloch et al, 2006;Yu et al, 2007).…”

Section: Alpha-synuclein-positive Pathways Innervating the Gutsupporting

confidence: 79%

“…Alpha-synuclein is widely, but not universally, expressed in the CNS (Li et al, 2002;Brenz Verca et al, 2003;Adamczyk et al, 2005;Yu et al, 2007). Furthermore, though the patterns are less thoroughly characterized for the periphery, the protein is also expressed in some elements of the peripheral autonomic nervous system (Bloch et al, 2006;Braak et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?

et al. 2008

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The protein alpha-synuclein is implicated in the development of Parkinson's disease. The molecule forms Lewy body aggregates that are hallmarks of the disease, has been associated with the spread of neuropathology from the peripheral to the central nervous system, and appears to be involved with the autonomic disorders responsible for the gastrointestinal (GI) symptoms of individuals afflicted with Parkinson's. To characterize the normative expression of alpha-synuclein in the innervation of the GI tract, we examined both the postganglionic neurons and the preganglionic projections by which the disease is postulated to retrogradely invade the CNS. Specifically, in Fischer 344 and Sprague Dawley rats, immunohistochemistry in conjunction with injections of the tracer DextranTexas Red was used to determine, respectively, the expression of alpha-synuclein in the myenteric plexus and in the vagal terminals. Alpha-synuclein is expressed in a subpopulation of myenteric neurons, with the proportion of positive somata increasing from the stomach (~3%) through duodenum (proximal, ~6%; distal, ~13%) to jejunum (~22%). Alpha-synuclein is co-expressed with the nitrergic enzyme NOS or the cholinergic markers calbindin and calretinin in regionally specific patterns: ~90% of forestomach neurons positive for alpha-synuclein express NOS, whereas ~92% of corpus-antrum neurons positive for alpha-synuclein express cholinergic markers. Vagal afferent endings in the myenteric plexus and the GI smooth muscle do not express alpha-synuclein, whereas, virtually all vagal preganglionic projections to the gut express alpha-synuclein, both in axons and in terminal varicosites in apposition with myenteric neurons. Vagotomy eliminates most, but not all, alpha-synuclein-positive neurites in the plexus. Some vagal preganglionic efferents expressing alphasynuclein form varicose terminal rings around myenteric plexus neurons that are also positive for the protein, thus providing a candidate alpha-synuclein-expressing pathway for the retrograde transport of putative Parkinson's pathogens or toxins from the ENS to the CNS.

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Section: Alpha-synuclein-positive Pathways Innervating the Gutsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?

et al. 2008

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“…Brains were rapidly frozen in OCT embedding medium, and frozen sections with a thickness of 20 μm were taken through the hippocampus and processed in free-floating conditions. Immunohistochemical procedures were performed as described previously (Yu et al 2007) with slight modifications. Sections were treated with 0.1 M phosphatebuffered saline containing 0.3 % Triton X-100 (PBST) for 4 days and first incubated with the primary antibodies against α-synuclein (anti-α-synuclein monoclonal antibody 3D5 was kindly provided by Dr.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Sections were treated with 0.1 M phosphatebuffered saline containing 0.3 % Triton X-100 (PBST) for 4 days and first incubated with the primary antibodies against α-synuclein (anti-α-synuclein monoclonal antibody 3D5 was kindly provided by Dr. Shun Yu because this antibody recognizes amino acids 115-121 of α-synuclein both in synapses and nuclei, Yu et al 2007) overnight at 4°C. HSP70 antibody from Santa Cruz was used in this experiment.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Icariin reduces α-synuclein over-expression by promoting α-synuclein degradation

Zhang

Shen

Chu

et al. 2015

AGE

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The objectives of this study are to investigate the effects of icariin (a main component extracted from Epimedium) on over-expression of α-synuclein and to explore the underlying mechanisms. APPV717I transgenic (Tg) mice and A53T α-synuclein-transfected PC12 cells were used in this study. The content of α-synuclein mRNA was determined by reversetranscription PCR (RT-PCR). Western blotting and immunohistochemistry were used to detect the protein expression of α-synuclein, parkin, ubiquitin carboxyterminal hydrolase L1 (UCH-L1), and heat shock protein 70 (HSP70). In 10-month-old APP Tg mice, α-synuclein expression was increased, and the expression of Parkin, UCH-L1, and HSP70 was decreased in the hippocampus. Intragastrical administration of icariin (30 and 100 μmol/kg) for 6 months (from 4 to 10 months old) decreased α-synuclein expression and increased the expression of Parkin, UCH-L1, and HSP70 in the hippocampus of APP Tg mice. Incubation of icariin (40 and 80 μM) with A53T α-synuclein-transfected PC12 cells for 24 h showed no difference in the expressions of α-synuclein mRNA among model group and icariintreated groups, but decreased α-synuclein protein expression in both monomer and tetramer. Along with the downregulation of α-synuclein, icariin (40 and 80 μM) elevated the expression of Parkin, UCH-L1, and HSP70 in A53T α-synuclein-transfected cells. Icariin inhibited the over-expression of α-synuclein both in vivo and in vitro. The mechanism of icariin may be related to upregulate Parkin and UCH-L1 expression in ubiquitinproteasome system and HSP70 in molecular chaperone, thus enhancing the degradation of α-synuclein. It is suggested that icariin may have the potential to treat Alzheimer's disease (AD) and other synucleinopathies.

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“…α-Synuclein is a highly soluble, heat-stable and natively unfolded protein [2,3] predominantly expressed in the neurons of the central nervous system. It is localized at presynaptic terminals in close proximity to synaptic vesicles [1,[4][5][6], as well as in the neuronal nuclei [7]. Recently, interactions between α-synuclein and dopamine (DA) have been vigorously studied [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Dopamine cannot promote oligomerization of unoxidized <i>α</i>-synuclein

Shimotakahara¹,

Matsui²,

Sakuma³

et al. 2013

JBPC

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Extensive nuclear localization of α-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody

Cited by 169 publications

References 54 publications

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?

Icariin reduces α-synuclein over-expression by promoting α-synuclein degradation

Dopamine cannot promote oligomerization of unoxidized <i>α</i>-synuclein

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Extensive nuclear localization of α-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody

Cited by 169 publications

References 54 publications

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?

Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?

Icariin reduces α-synuclein over-expression by promoting α-synuclein degradation

Dopamine cannot promote oligomerization of unoxidized &lt;i&gt;α&lt;/i&gt;-synuclein

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Dopamine cannot promote oligomerization of unoxidized <i>α</i>-synuclein