Disease relevance of Snca

• Moreover, its metabolism is perturbed in all cases of Parkinson's disease where alpha-synuclein accumulates in a filamentous form in the Lewy body nerve cell lesion [1].
• Differentiated PC12 cell lines expressing mutant alpha-synuclein showed decreased activity of proteasomes without direct toxicity [2].
• To address the role of alpha-synuclein in neurodegenerative diseases, we performed a yeast two-hybrid screen of a rat adult brain cDNA library using rat alpha-synuclein 2 (alphaSYN2) [3].
• Although a neuronal protein, alpha-synuclein is a major component of glial cytoplasmic inclusions (GCIs) in oligodendrocytes of multiple system atrophy (MSA) brains [4].
• Ultrastructure of alpha-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells [5].

Psychiatry related information on Snca

• Human alpha-synuclein was identified on the basis of proteolytic fragments derived from senile plaques of Alzheimer's disease, and it is the locus of mutations in some familial forms of Parkinson's disease [6].
• Secondly, alpha-synuclein is present in Lewy bodies of affected nerve cells in the predominant sporadic type of Parkinson's disease as well as in dementia with Lewy bodies [7].

High impact information on Snca

• Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha-synuclein [8].
• In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, alpha-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning [9].
• Similar to alpha-synuclein mRNA levels, protein levels in the hippocampus were higher in iP rats than iNP rats [10].
• Total gene expression analysis (TOGA) was used to identify genes that are differentially expressed in brain regions between the alcohol-naive, inbred alcohol-preferring (iP), and -nonpreferring (iNP) rats. alpha-Synuclein, expressed at >2-fold higher levels in the hippocampus of the iP than the iNP rat, was prioritized for further study [10].
• alpha-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats [10].

Chemical compound and disease context of Snca

• Mutations in the alpha-synuclein and parkin genes cause heritable forms of Parkinson's disease [11].
• alpha-, beta-, and gamma-Synuclein, a novel family of neuronal proteins, has become the focus of research interest because alpha-synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease [12].
• Our data illustrate the selective neurotoxic effect of NAC for dopaminergic neurons and support the central role of alpha-synuclein in the pathogenesis of Parkinson's disease [13].
• Alpha-synuclein protein is not scavenged in neuronal loss induced by kainic acid or focal ischemia [14].

Biological context of Snca

• Alpha-synuclein is a presynaptic protein that normally participates in the homeostasis of synaptic vesicles [1].
• Furthermore, the cytoprotective effect of parkin on alpha-synuclein-induced cell death was not inhibited in the presence of a proteasome inhibitor [11].
• Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis [2].
• Two point mutations in the alpha-synuclein gene are associated with autosomal-dominant Parkinson's disease (FPD) [15].
• We investigated the modulation of the messenger RNA encoding the amyloid precursor protein (APP) and alpha-synuclein following induction of long-term potentiation (LTP) in the dentate gyrus of young and aged rats [16].

Anatomical context of Snca

• Alpha-synuclein was robustly distributed in the substantia nigra pars reticulata, but was very weak or virtually absent from the perikarya of the neurons in the pars compacta [1].
• Alpha-synuclein was not observed in perikarya, but was distributed with high intensity in nerve terminals in the caudate and putamen and ventral pallidum, where beta-synuclein was much weaker and less densely distributed in the caudate and putamen [1].
• Our results indicated that mRNA expression and immunoreactivity of ASN is similar in brain cortex, hippocampus and striatum but markedly lower in cerebellum comparing to the other brain parts [17].
• Interestingly, in the hypothalamus the levels of alpha-synuclein remained decreased after 21 days post treatment perhaps due to regional differences in the PCBs elimination or perhaps a more specific interaction with the dopaminergic cells that are present in the hypothalamus that needs to be investigated further [18].
• The immunoreactivity of ASN in synaptic plasma membranes (SPM) from aged brain cortex, hippocampus and cerebellum is significantly lower comparing to adult by 39%, 24% and 65%, respectively [17].

Associations of Snca with chemical compounds

• Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain [18].
• We established inducible PC12 cell lines in which wild-type or mutant alpha-synuclein can be de-repressed by removing doxycycline [2].
• The induction of amyloid precursor protein and alpha-synuclein in rat hippocampal astrocytes by diethyldithiocarbamate and copper with or without glutathione [19].
• Furthermore, the absence of alpha-synuclein did not influence the percentage of lactacystin-treated neurons harboring cytoplasmic ubiquitinated inclusions or alter the solubility of such inclusions [20].
• We investigated the neurotoxic activity of the nonamyloid component (NAC) of senile plaque, the fibrillogenic fragment (61-95) of alpha-synuclein, in vitro and in vivo [13].

Physical interactions of Snca

• Rat alpha-synuclein interacts with Tat binding protein 1, a component of the 26S proteasomal complex [3].

Enzymatic interactions of Snca

• Parkin cleaves intracellular alpha-synuclein inclusions via the activation of calpain [11].

Regulatory relationships of Snca

• alpha-synuclein overexpression promotes aggregation of mutant huntingtin [21].
• Application of basic Fibroblast growth factor (bFGF) promoted alpha-synuclein expression selectively within dopaminergic, and not GABAergic or cortical neurons [22].
• Endogenous alpha-synuclein is induced by valproic acid through histone deacetylase inhibition and participates in neuroprotection against glutamate-induced excitotoxicity [23].

Other interactions of Snca

• The rank order of mRNA levels in different structures was cortex = hippocampus > striatum > cerebellum for alpha-synuclein; cortex > hippocampus = cerebellum > striatum for beta-synuclein; and hippocampus = striatum > cortex = cerebellum for gamma-synuclein [24].
• The decrease in alpha-synuclein was accompanied by a transient increase in parkin and synaptophysin levels [18].
• The results showed that Aroclor did not cause changes in the expression and processing of APP but at a dose 100 microg/g/day repeated for 6 days caused a decrease in the expression of alpha-synuclein in the cerebellum, cortex, hippocampus and hypothalamus of the animals sacrificed 2 days after treatment [18].
• In addition, alpha-synuclein was intense in the vagus nucleus, but weak in the oculomotor, facial, hypoglossal, accessory and ambiguous nuclei, where beta-synuclein was very intensely present [1].
• Therefore, the objective of the present study was to investigate the potential contribution of alterations in the caveolar system in mediating alpha-synuclein effects on the ERK signaling pathway [25].

Analytical, diagnostic and therapeutic context of Snca

• In the present study we investigated the expression of ASN mRNA and protein in the different brain parts of the adult (4-month-old) and aged (24-month-old) rats by using RT-PCR technique and Western blot, respectively [17].
• In situ hybridization was used to determine specific brain regions and cells expressing alpha-synuclein in the iP and iNP rats [10].
• Atomic force microscopy (AFM) revealed two distinct forms of protofibrillar alpha-synuclein: rapidly formed spherical protofibrils and annular protofibrils, which were produced on prolonged incubation of spheres [15].
• In contrast, the amount of alpha-synuclein protein, as determined by immunoblotting, continued to increase throughout development and remained at a high level for at least two years [26].
• Using in situ hybridization and an S1 nuclease protection assay, we found a high expression of alpha-synuclein messenger RNA during early postnatal development, followed by a marked decrease between postnatal days 14 and 93 [26].

References